bluuebunny/crossref_metadata_2025 huggingface dataset:
The aroylhydrazone INHHQ prevents memory impairment induced by Alzheimer’s-linked amyloid-β oligomers in mice
Authors: De Falco Anna , Kincheski Grasielle C. , Atrián-Blasco Elena , Hureau Christelle , Ferreira Sergio T. , Rey Nicolás A.
Published: August 2020

Converging evidence indicates that neurotoxicity and memory impairment in Alzheimer’s disease is induced by brain accumulation of soluble amyloid-β oligomers (AβOs). Physiological metals are poorly distributed and concentrated in the senile plaques typical of Alzheimer’s disease, where they may be coordinated to the amyloid-β peptide (Aβ). Indeed, zinc and copper increase Aβ oligomerization and toxicity. Metal-protein attenuating compounds represent a class of agents proposed for Alzheimer’s disease treatment, as they reduce abnormal interactions of metal ions with Aβ, inhibit Aβ oligomerization and prevent deleterious redox reactions in the brain. The present work investigates the protective action of an isoniazid-derived aroylhydrazone, INHHQ, on AβO-induced memory impairment. Systemic administration of a single dose of INHHQ (1 mg/kg) prevented both short-term and long-term memory impairment caused by AβOs in mice. In-vitro studies showed that INHHQ prevents Cu(Aβ)-catalyzed production of reactive oxygen species. Although the mechanism of protection by INHHQ is not yet fully understood at a molecular level, the results reported herein certainly point to the value of aroylhydrazones as promising neuroprotective agents in Alzheimer’s disease and related disorders.
The Feeling of Emptiness: A Review of a Complex Subjective Experience
Authors: D’Agostino Alessandra , Pepi Raffaele , Rossi Monti Mario , Starcevic Vladan
Published: August 2020

A feeling of emptiness is commonly encountered in clinical practice, but it is poorly understood, with incongruent approaches to its definition and possible role in various disorders. This review examines the conceptualization of the feeling of emptiness and its place in psychopathology. We found an imbalance between theoretical approaches to this phenomenon and empirical research, and argue that more studies using adequate assessment tools are needed. Based on our literature review, we propose that a feeling of emptiness is a complex, negative emotional state that is experienced in different ways by different individuals. This feeling includes a physical or bodily component, a component of aloneness or social disconnectedness, and a component of a deep sense of personal unfulfillment or lack of purpose. The feeling of emptiness is related to other emotional states (dysphoria, boredom, loneliness, and numbness) and overlaps to some extent with them. Although the feeling of emptiness is most often considered in the context of borderline personality disorder, it is also encountered in depression, narcissistic personality disorder, and schizophrenia spectrum disorders, with its features potentially varying between different conditions. The feeling of emptiness may lead to nonsuicidal self-injury and may also have an important relationship with suicidality. We conclude by offering suggestions for further research, emphasizing a need to refine the multidimensional conceptualization of the feeling of emptiness and to better understand its manifestations and relationships with other emotions within various forms of psychopathology.
Presentation, Diagnostic Evaluation, Management, and Rates of Serious Bacterial Infection in Infants With Acute Dacryocystitis Presenting to the Emergency Department
Authors: Harris Holly K. , Harper Marvin , Kimia Amir
Published: August 2020

Background:

Dacryocystitis is considered benign, yet infants represent a population at risk of complications. The presentation, management, and rates of serious bacterial infection in infants with dacryocystitis have not been described.

Methods:

We conducted a retrospective study of infants (12 months or younger) presenting to a single urban tertiary care pediatric emergency department between January 1995 and March 2014 with concern for dacryocystitis. Exclusion criteria included immune compromise or craniofacial anomalies. Cases were identified using text search software, followed by manual chart review.

Results:

We identified 333 subjects, and median age was 38 days (interquartile range, 12; 106). Fifty-three percent were female. Most were afebrile (81%, T < 38°C) at triage while 6% had fever of ≥39°C. Two of 135 blood cultures sent were positive (both Streptococcus pneumoniae). Lumbar punctures were performed on 40 patients (12%), and no cerebrospinal fluid (CSF) cultures were positive. Eye cultures were positive in 47% (N = 58) of infants cultured (N = 123); the most common pathogens were Haemophilus species (N = 17), Staphylococcus aureus (N = 13), Gram-negative rods (N = 7), and Moraxella species (N = 4). Imaging was obtained in 11 subjects (3.3%) with 3 demonstrating cellulitis and 1 a hemangioma. Ophthalmology was consulted for 21%, and an intervention/probe performed in 6%. Topical antibiotics were used in 147 subjects (44%), oral antibiotics in 100 (33%), and parenteral antibiotics in 87 (26%).

Conclusion:

Infants with dacryocystitis have a variable presentation and management ranges from observation to aggressive management. The rates of serious bacterial infection were low in this sample and not associated with any presenting risk factors.
Efficacy of Triamcinolone-Soaked Nasal Packing on Endoscopic Dacryocystorhinostomy
Authors: Kang Tae Seen , Won Yeo Kyoung , Kim Jung Yeul , Kim Kyoung Nam , Lee Sung Bok
Published: August 2020

Purpose:

To evaluate the efficacy of triamcinolone-soaked nasal packing in endoscopic dacryocystorhinostomy (EDCR).

Methods:

Patients who underwent EDCR between September 2012 and August 2017 were included. They were assigned to triamcinolone (201 eyes) or control (206 eyes) group based on the order of surgery. Granulation occurrence and outcome were assessed at 3 and 6 months postoperatively, respectively.

Results:

The success rates were 94.3% (overall anatomical success), 90.4% (complete anatomical success), 92.1% (overall functional success), and 76.7% (complete functional success). The overall functional success rate was significantly higher in the triamcinolone group (95.0% vs. 89.3%, p = 0.033). The overall anatomical success rate (96.0% vs. 92.7%, p = 0.149) and complete functional success rate (79.6% vs. 73.8%, p = 0.166) were also higher in the triamcinolone group, but this difference was not statistically significant. Granulation occurred in 62 eyes (15.2%); the incidence was significantly lower in the triamcinolone group (10.0% vs. 20.4%, p = 0.003).

Conclusion:

The authors suggest that use of triamcinolone-soaked nasal packing in EDCR is effective in significantly reducing the incidence of postoperative granulation and epiphora.
Postoperative serum carcinoembryonic antigen levels cannot predict survival in colorectal cancer patients with type II diabetes
Authors: Huang Chih-Sheng , Chen Chin-Yau , Huang Li-Kuo , Wang Wei-Shu , Yang Shung-Haur
Published: August 2020

Background:

Most clinical guidelines recommend measuring postoperative carcinoembryonic antigen (CEA) levels to predict the prognosis of colorectal cancer. However, type II diabetes can increase serum CEA levels which may bias the prognosis. Thus, we aimed to evaluate the impact of type II diabetes on CEA prognostic accuracy in colorectal cancer.

Methods:

This retrospective cohort study included 407 patients who underwent curative resection for stage I to III colorectal adenocarcinoma in a single institution between January 2010 and June 2018. The patients were categorized into two groups according to their postoperative serum CEA levels: group A <5.0 ng/mL (n = 341) and group B ≥5.0 ng/mL (n = 66). Patients were also categorized into two subgroups according to their history of type II diabetes: patients with type II diabetes mellitus (n = 112) and patients without type II diabetes (n = 295).

Results:

The 3-year disease-free survival (DFS) rates were significantly higher in patients with normal postoperative CEA (group A, 83.8%) than in patients with elevated preoperative and postoperative CEA (group B, 63.6%) (p < 0.001). However, although patients with type II diabetes mellitus had higher postoperative CEA levels than those without type II diabetes mellitus (3.1 vs 2.5 ng/mL, p < 0.001), group B patients with type II diabetes mellitus had a significantly higher 3-year DFS rate than those without type II diabetes mellitus (80.0% vs 55.6%, p = 0.003).

Conclusion:

Type II diabetes was associated with higher preoperative and postoperative CEA levels in patients with colorectal cancer. Consequently, elevated postoperative CEA level was not associated with shorter 3-year DFS in patients with type II diabetes, as opposed to patients without type II diabetes. Therefore, colorectal cancer patients with type II diabetes may need alternative tumor markers to be used during the surveillance strategy after curative surgery.
A statistical predictive model consistent within a 5-year follow-up period for patients with acute heart failure
Authors: Guo Chao-Yu , Chan Chien-Hui , Chou Yu-Chin , Sung Shih-Hsien , Cheng Hao-Min
Published: August 2020

Background:

Acute heart failure (AHF) is a major and rapidly growing health problem responsible for millions of hospitalizations annually. Due to a high proportion of in-hospital mortality and postdischarge rehospitalization and mortality, a prompt strategy for risk stratification and subsequently tailored therapy is desirable to help improve clinical outcomes. The AHEAD (A: atrial fibrillation; H: hemoglobin; E: elderly; A: abnormal renal parameters; D: diabetes mellitus) and AHEAD-U (A: atrial fibrillation; H: hemoglobin; E: elderly; A: abnormal renal parameters; D: diabetes mellitus, U: uric acid) are popular prognostic scoring systems. However, only a specific follow-up period is considered in these systems, and whether their predictive capability is still accurate in a significantly shorter or longer follow-up period is not known.

Methods:

In this research, we adapted extensive statistical approaches based on the Cox model to explore consistent risk factors in various follow-up durations. Results showed that six factors, namely, hemoglobin level, age, sodium level, blood urea nitrogen level, atrial fibrillation, and high-density lipoprotein level could be used to establish a new prognostic model, which was referred to as HANBAH. For a simple clinical application, the HANBAH scoring system, with scores from 0 to 6, was developed using several statistical models.

Results:

Based on an evaluation using the conventional statistical approaches, such as the Akaike information criterion, concordance statistic, and Cox area under the curve, the HANBAH scoring system consistently outperformed other strategies in predicting short- and long-term mortality. Notably, an independent replication study also revealed similar results. In addition, a modern machine learning technique using the support vector machine confirmed its superior performance.

Conclusion:

The use of the HANBAH scoring system, which is a clinically friendly tool, was proposed, and its efficacy in predicting the mortality rates of patients with AHF regardless of the follow-up duration was independently validated.
Hashimoto's thyroiditis as a risk factor for thyroid cancer
Authors: Feldt-Rasmussen Ulla
Published: August 2020

Purpose of review

To summarize the recent developments in considering Hashimoto's thyroiditis as a risk factor for thyroid cancer.

Recent findings

Modern approaches to understanding the co-occurrence of Hashimoto's thyroiditis and thyroid cancer have consistently found increased prevalence of both conditions, separately as well as of their coexistence. The inflammatory process in Hashimoto's thyroiditis is understood as a potential risk factor for thyroid cancer development. This has also provided a better understanding of the limitations in the current diagnostic and follow-up armamentarium for both conditions, resulting in international guidelines from the clinical and scientific societies. Other recent developments call for a paradigm shift in guidelines on thyroid carcinomas when lymphocytic infiltration is present, which potentially should always be considered the case at least in areas of sufficient iodine intake.

The literature of Hashimoto's thyroiditis as a risk factor for thyroid cancer is reviewed over the last year to highlight new developments in the understanding of their association and future clinical implications.
Multimodal imaging of thyroid cancer
Authors: Brauckhoff Katrin , Biermann Martin
Published: August 2020

Purpose of review

Thyroid cancer is the most common endocrine cancer in adults with rising incidence. Challenges in imaging thyroid cancer are twofold: distinguishing thyroid cancer from benign thyroid nodules, which occur in 50% of the population over 50 years; and correct staging of thyroid cancer to facilitate appropriate radical surgery in a single session. The clinical management of thyroid cancer patients has been covered in detail by the 2015 guidelines of the American Thyroid Association (ATA). The purpose of this review is to state the principles underlying optimal multimodal imaging of thyroid cancer and aid clinicians in avoiding important pitfalls.

Recent findings

Recent additions to the literature include assessment of ultrasound-based scoring systems to improve selection of nodules for fine needle biopsy (FNB) and the evaluation of new radioactive tracers for imaging thyroid cancer.

The mainstay of diagnosing thyroid cancer is thyroid ultrasound with ultrasound-guided FNB. Contrast-enhanced computed tomography and PET with [18F]-fluorodeoxyglucose (FDG) and MRI are reserved for advanced and/or recurrent cases of differentiated thyroid cancer and anaplastic thyroid cancer, while [18F]FDOPA and [68Ga]DOTATOC are the preferred tracers for medullary thyroid cancer.
Fibroblasts in atherosclerosis: heterogeneous and plastic participants
Authors: Tillie Renée J.H.A. , van Kuijk Kim , Sluimer Judith C.
Published: August 2020

Purpose of review

Fibroblasts are very heterogeneous and plastic cells in the vasculature. A growing interest in fibroblasts in healthy and atherosclerotic vasculature is observed, next to macrophages, endothelial cells, and smooth muscle cells (SMCs). In this review, we discuss fibroblast presence, heterogeneity, origin, and plasticity in health and atherosclerosis based on latest literature.

Recent findings

With help of single cell sequencing (SCS) techniques, we have gained more insight into presence and functions of fibroblasts in atherosclerosis. Next to SMCs, fibroblasts are extracellular matrix-producing cells abundant in the vasculature and involved in atherogenesis. Fibroblasts encompass a heterogeneous population and SCS data reveal several fibroblast clusters in healthy and atherosclerotic tissue with varying gene expression and function. Moreover, recent findings indicate interesting similarities between adventitial stem and/or progenitor cells and fibroblasts. Also, communication with inflammatory cells opens up a new therapeutic avenue.

Because of their highly plastic and heterogeneous nature, modulating fibroblast cell function and communication in the atherosclerotic vessel might be useful in battling atherosclerosis from within the plaque.
Transport of LDLs into the arterial wall: impact in atherosclerosis
Authors: Zhang Xinbo , Fernández-Hernando Carlos
Published: August 2020

Purpose of review

Atherosclerosis is a complicated cardiovascular disease characterized by unbalanced lipid metabolism and unresolved inflammation that occurred inside of arteries. The transcytosis of LDL across the endothelium and its accumulation in the arterial wall is the initial step of atherosclerosis. Here, we summarize recent research into the understanding of the regulatory mechanisms of endothelial LDL transcytosis and its relevance in the development of atherosclerosis.

Recent findings

A number of recent studies have revealed the contribution of caveolae, activin-like kinase 1 (ALK1) or scavenger receptor B1 (SR-B1) in endothelial LDL transcytosis and the progression of atherosclerosis. Caveolin-1 (Cav-1), the major protein component in caveolae, is required for the formation of caveolae and caveolae-mediated LDL uptake and transcytosis across the endothelium. SR-B1 and ALK1 directly bind LDL and facilitate the transport of LDL through the endothelial cells. The change in expression of caveolae-associated proteins and SR-B1 regulates endothelial LDL transcytosis and the pathogenesis of atherosclerosis.

Caveolae, ALK1 and SR-B1 are identified as key regulators in the LDL transcytosis across the endothelium. Endothelial LDL transcytosis might be a potential therapeutic approach to limit the initiation of early atherosclerosis and treat the atherosclerotic vascular diseases.
Age-associated arterial calcification: the current pursuit of aggravating and mitigating factors
Authors: Chakrabarti Apurba , Goldstein Daniel R. , Sutton Nadia R.
Published: August 2020

Purpose of review

The incidence of arterial calcification increases with age, can occur independently of atherosclerosis and hyperlipidemia, contributes to vessel stiffening, and is associated with adverse cardiovascular outcomes. Here, we provide an up-to-date review of how aging leads to arterial calcification and discuss potential therapies.

Recent findings

Recent research suggests that mitochondrial dysfunction (impaired efficiency of the respiratory chain, increased reactive oxygen species production, and a high mutation rate of mitochondrial DNA), cellular senescence, ectonucleotidases, and extrinsic factors such as hyperglycemia promote age-determined calcification. We discuss the future potential impact of antilipidemics, senolytics, and poly(ADP-ribose)polymerases inhibitors on age-associated arterial calcification.

Understanding how mechanisms of aging lead to arterial calcification will allow us to pinpoint prospective strategies to mitigate arterial calcification, even after the effects of aging have already begun to occur.
Pancreatic complications in children with cystic fibrosis
Authors: Sellers Zachary M.
Published: August 2020

Purpose of review

The pancreas is highly affected in cystic fibrosis, with complications occurring early in childhood. This review highlights recent research in exocrine pancreatic function in the era of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies and discusses how these are affecting pancreatitis and exocrine pancreatic insufficiency (EPI) in children. Additionally, new research into exocrine--endocrine interactions sheds light on how CFTR dysfunction in ductal cells may affect beta cells.

Recent findings

Ivacaftor has disproved the hypothesis that EPI in children with cystic fibrosis is irreversible. Improvements in pancreatic function have increased pancreatitis episodes in some children and reduced them in others. Imaging advances are providing complementary methods for exocrine pancreatic function testing. New research into the interplay between the exocrine and endocrine components of the pancreas are elucidating the intertwined and complex relationship between the exocrine and endocrine pancreas.

Pancreatic complications contribute to the morbidity and mortality of children with cystic fibrosis. Increasing use of highly effective CFTR modulators will not only abrogate these but will also advance our understanding of pancreatic pathophysiology in cystic fibrosis. New frontiers into pancreatic gene therapy and exocrine--endocrine research will help provide new therapeutic opportunities for pancreatitis, EPI, and diabetes in cystic fibrosis.
Evaluating Feasibility of Personal Diabetes Device Data Collection for Research
Authors: Faulds Eileen R. , Militello Lisa K. , Tubbs-Cooley Heather , Happ Mary Beth
Published: August 2020

Background

Diabetes devices, like insulin pumps and continuous glucose monitors (CGMs), capture and store patient adherence and utilization data that can be retrieved or downloaded providing objective information on self-management behaviors; yet, diabetes device data remain underutilized in research.

Objective

The aim of the study was to examine the usability and feasibility of personal diabetes device data collected using a clinical download platform retooled for research purposes.

Methods

Investigators evaluated the feasibility of raw diabetes device data collection. One hundred eight preteens and adolescents with Type 1 diabetes and their parents provided consent/assent.

Results

Data were successfully collected from the diabetes devices (insulin pumps and CGM) of 97 youth using a clinical download software adapted for research, including data from all three commercially available CGM systems and insulin pumps brands, which contained all current and previous models of each insulin pump brand. The time required to download, mode of connection, and process varied significantly between brands. Despite the use of an agnostic download software, some outdated device brands and cloud-based CGM data were unsupported during data collection. Within the download software, dummy clinical accounts were created for each study participant, which were then linked back to a master study account for data retrieval. Raw device data were extracted into seven to eight Excel files per participant, which were then used to develop aggregate daily measures.

Discussion

Our analysis is the first of its kind to examine the feasibility of raw diabetes device data using a clinical download software. The investigators highlight issues encountered throughout the research process, along with mitigating strategies to inform future inquiry.

Conclusion

This study demonstrates the feasibility of raw data collection, from a wide variety of insulin pump and CGM brands, through the retooling of a clinical download software. Data from these personal devices provide a unique opportunity to study self-management behavior and the glycemic response of individuals in their everyday environments.
Characteristics of Women and Their Male Sex Partners Predict Bacterial Vaginosis Among a Prospective Cohort of Kenyan Women With Nonoptimal Vaginal Microbiota
Authors: Mehta Supriya Dinesh , Agingu Walter , Nordgren Rachel K. , Green Stefan J. , Bhaumik Dulal K. , Bailey Robert C. , Otieno Fredrick
Published: August 2020

Background

Up to 50% of women with nonoptimal vaginal microbial community state type (CST) have bacterial vaginosis (BV). Little is known about what distinguishes women with and without BV diagnosis within nonoptimal CST. We identified features of women and their male sex partners associated with BV among women with nonoptimal vaginal CST.

Methods

In this prospective study, 252 heterosexual couples were observed at 1, 6, and 12 months after baseline. Microbiomes were characterized in cervicovaginal lavage and penile meatal swabs through high-throughput 16s ribosomal RNA gene amplicon sequencing. Nonoptimal CST was defined as CST-IV. Bacterial vaginosis was defined as a Nugent score of 7 to 10. Generalized estimating equation analysis estimated adjusted odds ratios (aORs) for BV among women with nonoptimal CST.

Results

At baseline, women with nonoptimal CST were a median age of 22 years, 44% had BV, 16% had HIV, and 66% had herpes simplex virus (HSV) type 2. Male partners were a median age of 27 years, 12% had HIV, 48% had HSV-2, and 55% were circumcised. Within nonoptimal CST,Sneathia sanguinegens,Prevotellaspecies,Prevotella amnii, and Clostridiales, BV-associated bacteria-2 were statistically significantly enriched in observations with BV. In multivariable generalized estimating equation controlling for CST, HIV, and HSV-2, BV was increased among women with CST-IVA (aOR, 1.91;P= 0.087), HIV (aOR, 2.30;P= 0.051), HSV-2 (aOR, 1.75;P= 0.065), and enrichment of male partner penile taxa:Dialister(aOR, 1.16;P= 0.034),Megasphaera(aOR, 1.22;P= 0.001), andBrevibacterium(aOR, 1.13;P= 0.019).

These results provide insights into factors differentiating women with BV among those with nonoptimal vaginal CST. Interrupting the sexual exchange of penile and vaginal taxa may be beneficial for preventing pathologic state of vaginal microbiome.
Fatal 4-MEC Intoxication
Authors: Braham Mohamed Yassine , Franchi Angélique , Cartiser Nathalie , Bévalot Fabien , Bottinelli Charline , Fabrizi Hervé , Fanton Laurent
Published: August 2020

Synthetic cathinones are one of the major pharmacological families of new psychoactive substances and 4-methylethcathinone (4-MEC) has emerged in recent years as a recreational psychostimulant. We report a case of a 35-year-old man found dead and naked at home by his friend. Although no anatomic cause of death was observed at autopsy, toxicological analysis identified 4-MEC and hydroxyzine at therapeutic level (160 ng/mL). 4-Methylethcathinone was quantified in autopsy samples by a validated method consisting in liquid-liquid extraction and gas chromatography coupled to tandem mass spectrometry: peripheral blood, 14.6 μg/mL; cardiac blood, 43.4 μg/mL; urine, 619 μg/mL; vitreous humor, right 2.9 μg/mL and left 4.4 μg/mL; bile, 43.5 μg/mL; and gastric content, 28.2 μg/mL. The cause of death was 4-MEC intoxication and the manner of death could be either accidental or suicidal. The literature concerning 4-MEC was reviewed, focusing on distribution in classical postmortem matrices and 4-MEC metabolism and postmortem redistribution and stability.
Frequent expression of activation-induced cytidine deaminase in diffuse large B-cell lymphoma tissues from persons living with HIV
Authors: Shponka Volodymyr , Reveles Candace Y. , Alam Sinthia , Jaramillo Melba , Maguire Alanna , Rimsza Lisa M. , Kendrick Samantha
Published: August 2020

Objective:

The increased risk for persons living with HIV to develop diffuse large B-cell lymphoma (DLBCL) even in the post-antiretroviral therapy eras suggests a role beyond immunosuppression in lymphoma development. However, the mechanisms leading to lymphoma in the HIV setting are not fully understood. HIV is known to induce activation-induced cytidine deaminase (AID) levels in nonneoplastic B cells in vitro and chronic AID expression may play an important role in lymphomagenesis. Although AID expression is observed in B-cell lymphoma, studies in HIV-associated DLBCL are limited.

Design:

In this study, we conducted a retrospective review of DLBCL tissues from patients with and without HIV infection to compare expression of AID and B-cell receptors potentially involved in HIV and B-cell interaction.

Methods:

We evaluated DLBCL formalin-fixed paraffin-embedded tissues from 72 HIV-seropositive and 58 HIV-seronegative patients for AID, DC-SIGN, and CD40 protein expression. BCL2 and MYC, two well established prognostically significant oncoproteins in DLBCL, were also assessed at the protein and mRNA levels. Subset analysis was performed according to DLBCL subtype and EBV status.

Results:

Of note, AID expression was more frequent in HIV-associated DLBCL compared with non-HIV-associated DLBCL regardless of cell-of-origin subtype, and also displayed significantly less BCL2 expression. Despite no direct correlation with AID expression, the HIV-DLBCL tissues also exhibited high levels of the DC-SIGN receptor.

Conclusion:

Collectively, these findings support a potential role for AID in the pathogenesis of HIV-associated lymphomas and suggest the need of further investigations into the involvement of the DC-SIGN receptor-signaling pathway.
Neurobehavioral outcomes in young adults with perinatally acquired HIV
Authors: Coutifaris Paulina , Byrd Desiree , Childs Jocelyn , Clark Uraina , Posada Roberto , Robbins Reuben , Morgello Susan
Published: August 2020

Background:

With combination antiretroviral therapy (cART), infants with perinatally acquired HIV (pHIV) are living into adolescence and adulthood. Worldwide, many have not received cART in the first years of life, and challenges of adolescence complicate transition to adulthood. Neurobehavioral outcomes in pHIV young adults (pHIVAd) are infrequently reported.

Objectives:

To examine neurobehavioral characteristics of pHIVAd ages 21—30 years, and to compare them with age-matched young adults infected in the second or third decade of life (HIVagematch), and older adults with similar duration HIV disease (HIVOA).

Methods:

A comprehensive neuropsychological test battery and questionnaires to determine cognitive function and mood, and reviews of neuromedical and behavioral records were undertaken in three groups of 13 individuals each. Descriptive analysis and bivariate techniques were used for comparisons.

Results:

Rates of cognitive impairment were highest in pHIVAd (85%) compared with HIVagematch (38%) and HIVOA (62%). pHIVAd had the worst scores in global cognition, speed of information processing, working memory, and verbal fluency (0.5--1.0 SD below other groups). There was a trend for higher rates of psychiatric dysfunction (predominantly mood disorders) in pHIVAd (85%) compared with HIV-agematch (46%) and HIVOA (54%). Only four pHIVAd reported employment or enrollment in school. Four had autoimmune disorders.

Conclusion:

These pHIVAd displayed high rates of cognitive, psychiatric, and autoimmune dysfunction, greater than age-matched or HIV duration-matched comparators. Although this small study is largely descriptive in nature, it suggests that a lack of cART in early life may result in long-term neurobehavioral and immune abnormalities manifesting into adulthood.
Deciphering the serological response to syphilis treatment in men living with HIV
Authors: Ren Melody , Szadkowski Leah , Walmsley Sharon L.
Published: August 2020

Objective:

To examine syphilis serology after treatment in people living with HIV. No unanimous guidelines exist in the era of increasing coinfection.

Design:

Retrospective review using a tertiary care clinic in Toronto from 2000 to 2017.

Methods:

The 2015 Centers for Diseases Control and Prevention syphilis guidelines were used to define an adequate serologic response. Cumulative distribution estimates and proportional hazards models accounting for interval censoring estimated the time to serologic response and seroreversion. Multistate models were used to investigate extended periods of serofast serology.

Results:

A total of 171 patients with syphilis met our inclusion criteria (16 primary, 53 secondary, 26 early latent, 46 late latent, 30 neurosyphilis). Serologic response was achieved by 12 months for 65 (94%) patients and by 12–18 months for four (6%) patients with primary/secondary syphilis. For latent and neurosyphilis, 94 (92%) achieved serologic response by 24 months and one (1%) at 24.1 months. 84 (49%) patients achieved seroreversion with a median (95% confidence interval) time of 2 (1.44, 2.68) years. Latent syphilis was associated with a lower likelihood of achieving serologic response [hazard ratio (HR) = 0.52, P = 0.05] and seroreversion (HR = 0.27, P < 0.001) compared with primary/secondary syphilis. The probability of moving from a new infection state to a serofast state within 1 year was high (0.65) but the 1-year probability of transitioning from a serofast state to seroreversion was low (0.27).

Conclusion:

The majority of people living with HIV infected with syphilis will achieve an adequate serologic response as per the Centers for Diseases Control and Prevention guidelines. Seroreversion was observed in about half but can take years to occur.
Correlation of serum hepatitis B core-related antigen with hepatitis B virus total intrahepatic DNA and covalently closed circular-DNA viral load in HIV–hepatitis B coinfection
Authors: Dezanet Lorenza N.C. , Maylin Sarah , Gabassi Audrey , Rougier Hayette , Miailhes Patrick , Lascoux-Combe Caroline , Chas Julie , Girard Pierre-Marie , Delaugerre Constance , Zoulim Fabien , Lacombe Karine , Boyd Anders
Published: August 2020

Objective:

To assess whether quantified hepatitis B core-related antigen (qHBcrAg) is a surrogate marker of intrahepatic replication in HIV and hepatitis B virus (HBV) coinfection.

Design:

Cross-sectional study of 31 HIV–HBV-infected patients (total liver biopsies, n = 38) from a well defined cohort.

Methods:

Spearman's rank correlation coefficients were calculated between qHBcrAg and intrahepatic markers of HBV replication [total intrahepatic-DNA, covalently closed circular (ccc) DNA, cccDNA : total intrahepatic-DNA ratio].

Results:

At biopsy, 22 (71.0%) patients were hepatitis B ‘e’ antigen (HBeAg)-positive, 22 (71.0%) had detectable plasma HBV-DNA, and 17 (54.8%) were treated with tenofovir. Median levels (interquartile range) of intrahepatic markers were as follows: HBV cccDNA (n = 34), 0.26 copies/cell (0.4–2.89); total intrahepatic-DNA (n = 38), 2.38 copies/cell (0.58–207.9), and cccDNA : total intrahepatic-DNA ratio (n = 34), 0.05 (interquartile range = 0.01–0.12). There was a significantly strong correlation between qHBcrAg and cccDNA in all patients (Rho = 0.65, P < 0.001), while a moderate correlation was observed between qHBcrAg and total intrahepatic-DNA (Rho = 0.57, P < 0.001) or cccDNA : total intrahepatic-DNA ratio (Rho = −0.45, P = 0.01). Similar findings were observed for HBeAg-positive patients and those with detectable HBV-DNA, with the exception of qHBcrAg and cccDNA or cccDNA : total intrahepatic-DNA ratio. In contrast, no significant correlation between qHBcrAg and any intrahepatic marker was observed in HBeAg-negative patients or those with undetectable HBV-DNA. No significant difference was observed in median qHBcrAg levels across liver fibrosis stages (P = 0.5).

Conclusion:

qHBcrAg is a potential surrogate marker of cccDNA in HIV–HBV coinfected patients, yet might be less useful with undetectable serum HBV-DNA or HBeAg-negative status. Whether qHBcrAg provides further clinical utility compared with other serological markers remains debatable.
The predictors of pain extent in people living with HIV
Authors: Sabin Caroline A. , Harding Richard , Bagkeris Emmanouil , Geressu Adam , Nkhoma Kennedy , Post Frank A. , Sachikonye Memory , Boffito Marta , Anderson Jane , Mallon Patrick W.G. , Williams Ian , Vera Jaime , Johnson Margaret A. , Babalis Daphne , Winston Alan
Published: August 2020

Objective:

To investigate the prevalence of widespread pain among people with HIV (PWH) and describe associations with antiretroviral therapy (ART) and markers of HIV disease stage.

Design:

Cross-sectional analysis of cohort study in the United Kingdom and Ireland.

Methods:

Pain information was collected during the baseline visit (conducted from 2013 to 2015) through a self-completed manikin identifying pain at 15 sites from five body regions. Pain was classified as widespread if reported at at least four regions and at least seven sites, or regional otherwise. Chi-squared tests, Kruskal–Wallis tests and ordinal logistic regression were used to consider associations between pain extent and sociodemographic and HIV-related factors.

Results:

Among the 1207 participants (614 PWH ≥ 50 years, 330 PWH < 50 years, 263 HIV-negative controls ≥50 years), pain was most commonly reported at the upper (left: 28.9%, right: 28.0%) and lower (left: 25.7%; right: 24.5%) leg, upper (18.6%) and lower (29.7%) back and shoulders (left: 16.0%; right: 16.8%). Widespread pain was more commonly reported in PWH than in HIV-negative controls (PWH ≥ 50 years: 18.7%; PWH < 50 years: 12.7%; HIV-negative ≥50 years: 9.5%) with regional pain reported in 47.6, 44.8 and 49.8%, respectively (global P = 0.001). In multivariable analyses, pain extent was greater in those with lower educational attainment, those exposed to more ART drugs, and those with a higher current CD4+ cell count but longer exposure to immunosuppression.

Conclusion:

Widespread pain is commonly reported in PWH and is associated with longer duration of exposure to HIV, immunosuppression and ART. Our findings call for greater awareness, and interventions to support the management, of pain in PWH.
Updates on defining and detecting diarrheagenic Escherichia coli pathotypes
Authors: Jesser Kelsey J. , Levy Karen
Published: August 2020

Purpose of review

Several types of Escherichia coli cause acute diarrhea in humans and are responsible for a large burden of disease globally. The purpose of this review is to summarize diarrheagenic Escherichia coli (DEC) pathotype definitions and discuss existing and emerging molecular, genomic, and gut microbiome methods to detect, define, and study DEC pathotypes.

Recent findings

DEC pathotypes are currently diagnosed by molecular detection of unique virulence genes. However, some pathotypes have defied coherent molecular definitions because of imperfect gene targets, and pathotype categories are complicated by hybrid strains and isolation of pathotypes from asymptomatic individuals. Recent progress toward more efficient, sensitive, and multiplex DEC pathotype detection has been made using emerging PCR-based technologies. Genomics and gut microbiome detection methods continue to advance rapidly and are contributing to a better understanding of DEC pathotype diversity and functional potential.

DEC pathotype categorizations and detection methods are useful but imperfect. The implementation of molecular and sequence-based methods and well designed epidemiological studies will continue to advance understanding of DEC pathotypes. Additional emphasis is needed on sequencing DEC genomes from regions of the world where they cause the most disease and from the pathotypes that cause the greatest burden of disease globally.
Outcomes in Kidney Transplantation Between Veterans Affairs and Civilian Hospitals
Authors: Kesseli Samuel J. , Samoylova Mariya L. , Moris Dimitrios , Connor Ashton A. , Schmitz Robin , Shaw Brian I. , Gloria Jared N. , Abraham Nader , McElroy Lisa M. , Sudan Debra L. , Knechtle Stuart J. , Barbas Andrew S.
Published: August 2020

Objective:

We sought to compare kidney transplantation outcomes between Veterans Affairs (VA) and non-VA transplant centers.

Summary Background Data:

Transplant care at the VA has previously been scrutinized due to geographic and systematic barriers. The recently instituted MISSION Act entered effect June 6th, 2019, which enables veteran access to surgical care at civilian hospitals if certain eligibility criteria are met.

Methods:

We evaluated observed-to-expected outcome ratios (O:E) for graft loss and mortality using the Scientific Registry of Transplant Recipients database for all kidney transplants during a 15-year period (July 1, 2001–June 30, 2016). Of 229,188 kidney transplants performed during the study period, 1508 were performed at VA centers (N = 7), 7750 at the respective academic institutions affiliated with these VA centers, and 227,680 at non-VA centers nationwide (N = 286).

Results:

Aggregate O:E ratios for mortality were lower in VA centers compared with non-VA centers at 1 month and 1 year (O:E = 0.27 vs 1.00, P = 0.03 and O:E = 0.62 vs 1.00, P = 0.03, respectively). Graft loss at 1 month and 1 year was similar between groups (O:E = 0.65 vs 1.00, P = 0.11 and O:E = 0.79 vs 1.00, P = 0.15, respectively). Ratios for mortality and graft loss were similar between VA centers and their respective academic affiliates. Additionally, a subgroup analysis for graft loss and mortality at 3 years (study period January 1, 2009–December 31, 2013) demonstrated no significant differences between VA centers, VA-affiliates, and all non-VA centers.

Conclusions:

Despite low clinical volume, VA centers offer excellent outcomes in kidney transplantation. Veteran referral to civilian hospitals should weigh the benefit of geographic convenience and patient preference with center outcomes.
Portable Automated Surveillance of Surgical Site Infections Using Natural Language Processing
Authors: Bucher Brian T. , Shi Jianlin , Ferraro Jeffrey P. , Skarda David E. , Samore Matthew H. , Hurdle John F. , Gundlapalli Adi V. , Chapman Wendy W. , Finlayson Samuel R. G.
Published: August 2020

Objectives:

We present the development and validation of a portable NLP approach for automated surveillance of SSIs.

Summary of Background Data:

The surveillance of SSIs is labor-intensive limiting the generalizability and scalability of surgical quality surveillance programs.

Methods:

We abstracted patient clinical text notes after surgical procedures from 2 independent healthcare systems using different electronic healthcare records. An SSI detected as part of the American College of Surgeons’ National Surgical Quality Improvement Program was used as the reference standard. We developed a rules-based NLP system (Easy Clinical Information Extractor [CIE]-SSI) for operative event-level detection of SSIs using an training cohort (4574 operative events) from 1 healthcare system and then conducted internal validation on a blind cohort from the same healthcare system (1850 operative events) and external validation on a blind cohort from the second healthcare system (15,360 operative events). EasyCIE-SSI performance was measured using sensitivity, specificity, and area under the receiver-operating-curve (AUC).

Results:

The prevalence of SSI was 4% and 5% in the internal and external validation corpora. In internal validation, EasyCIE-SSI had a sensitivity, specificity, AUC of 94%, 88%, 0.912 for the detection of SSI, respectively. In external validation, EasyCIE-SSI had sensitivity, specificity, AUC of 79%, 92%, 0.852 for the detection of SSI, respectively. The sensitivity of EasyCIE-SSI decreased in clean, skin/subcutaneous, and outpatient procedures in the external validation compared to internal validation.

Conclusion:

Automated surveillance of SSIs can be achieved using NLP of clinical notes with high sensitivity and specificity.
A statistically rigorous deep neural network approach to predict mortality in trauma patients admitted to the intensive care unit
Authors: Ahmed Fahad Shabbir , Ali Liaqat , Joseph Bellal A. , Ikram Asad , Ul Mustafa Raza , Bukhari Syed Ahmad Chan
Published: August 2020

BACKGROUND

Trauma patients admitted to critical care are at high risk of mortality because of their injuries. Our aim was to develop a machine learning-based model to predict mortality using Fahad-Liaqat-Ahmad Intensive Machine (FLAIM) framework. We hypothesized machine learning could be applied to critically ill patients and would outperform currently used mortality scores.

METHODS

The current Deep-FLAIM model evaluates the statistically significant risk factors and then supply these risk factors to deep neural network to predict mortality in trauma patients admitted to the intensive care unit (ICU). We analyzed adult patients (≥18 years) admitted to the trauma ICU in the publicly available database Medical Information Mart for Intensive Care III version 1.4. The first phase selection of risk factor was done using Cox-regression univariate and multivariate analyses. In the second phase, we applied deep neural network and other traditional machine learning models like Linear Discriminant Analysis, Gaussian Naïve Bayes, Decision Tree Model, and k-nearest neighbor models.

RESULTS

We identified a total of 3,041 trauma patients admitted to the trauma surgery ICU. We observed that several clinical and laboratory-based variables were statistically significant for both univariate and multivariate analyses while others were not. With most significant being serum anion gap (hazard ratio [HR], 2.46; 95% confidence interval [CI], 1.94–3.11), sodium (HR, 2.11; 95% CI, 1.61–2.77), and chloride (HR, 2.11; 95% CI, 1.69–2.64) abnormalities on laboratories, while clinical variables included the diagnosis of sepsis (HR, 2.03; 95% CI, 1.23–3.37), Quick Sequential Organ Failure Assessment score (HR, 1.52; 95% CI, 1.32–3.76). And Systemic Inflammatory Response Syndrome criteria (HR. 1.41; 95% CI, 1.24–1.26). After we used these clinically significant variables and applied various machine learning models to the data, we found out that our proposed DNN outperformed all the other methods with test set accuracy of 92.25%, sensitivity of 79.13%, and specificity of 94.16%; positive predictive value, 66.42%; negative predictive value, 96.87%; and area under the curve of the receiver-operator curve of 0.91 (1.45–1.29).

CONCLUSION

Our novel Deep-FLAIM model outperformed all other machine learning models. The model is easy to implement, user friendly and with high accuracy.

LEVEL OF EVIDENCE

Prognostic study, level II.
The elusive promise of myostatin inhibition for muscular dystrophy
Authors: Wagner Kathryn R.
Published: August 2020

Purpose of review

Recent terminations of clinical trials of myostatin inhibitors in muscular dystrophy have raised questions about the predictiveness of mouse models for this therapeutic strategy.

Recent findings

A variety of myostatin inhibitors have been developed for preclinical and clinical studies. These inhibitors have ameliorated the phenotype of many but not all mouse models of muscular dystrophy. However, randomized double-blinded placebo controlled trials in both pediatric and adult muscular dystrophies have, as of yet, not demonstrated functional improvement.

The present article will review the preclinical promise of myostatin inhibitors, the clinical trial experience to date of these inhibitors in muscular dystrophy, and the potential reasons for the lack of observed translation.
The role of the microbiome in host evolution
Authors: Kolodny Oren , Callahan Benjamin J. , Douglas Angela E.
Published: August 2020

In the last decade, we have witnessed a major paradigm shift in the life sciences: the recognition that the microbiome, i.e. the set of microorganisms associated with healthy animals (including humans) and plants, plays a crucial role in the sustained health and fitness of its host. Enabled by rapid advances in sequencing technologies and analytical methods, substantial advances have been achieved in both identifying the microbial taxa and understanding the relationship between microbiome composition and host phenotype. These breakthroughs are leading to novel strategies for improved human and animal health, enhanced crop yield and nutritional quality, and the control of various pests and disease agents.

This article is part of the theme issue ‘The role of the microbiome in host evolution'.
Symbiosis and stress: how plant microbiomes affect host evolution
Authors: Hawkes Christine V. , Bull James J. , Lau Jennifer A.
Published: August 2020

Existing paradigms for plant microevolution rarely acknowledge the potential impacts of diverse microbiomes on evolutionary processes. Many plant-associated microorganisms benefit the host via access to resources, protection from pathogens, or amelioration of abiotic stress. In doing so, they alter the plant's perception of the environment, potentially reducing the strength of selection acting on plant stress tolerance or defence traits or altering the traits that are the target of selection. We posit that the microbiome can affect plant microevolution via (1) manipulation of plant phenotypes in ways that increase plant fitness under stress and (2) direct microbial responses to the environment that benefit the plant. Both mechanisms might favour plant genotypes that attract or stimulate growth of the most responsive microbial populations or communities. We provide support for these scenarios using infectious disease and quantitative genetics models. Finally, we discuss how beneficial plant–microbiome associations can evolve if traditional mechanisms maintaining cooperation in pairwise symbioses, namely partner fidelity, partner choice and fitness alignment, also apply to the interactions between plants and diverse foliar and soil microbiomes. To understand the role of the plant microbiome in host evolution will require a broad ecological understanding of plant–microbe interactions across both space and time.

This article is part of the theme issue ‘The role of the microbiome in host evolution'.