bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Nicotine Dependence on the Risk of Developing Post-traumatic Stress Disorder: Results From the National Epidemiologic Survey on Alcohol and Related Conditions
Authors: Ibrahim Christine , Le Foll Bernard , Hassan Ahmed N
Published: November 2021

Introduction

It is evident that an association between smoking and post-traumatic stress disorder (PTSD) exists, but research is lacking in establishing the directionality of the relationship.

Aims and Methods

We used longitudinal data from waves I (2001–2002) and II (2004–2005) of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Individuals with nicotine dependence (ND) were matched to individuals without ND using propensity score matching to estimate the risk of developing PTSD after trauma. We also matched smokers (with or without ND) to lifetime nonsmokers to estimate their risk of developing PTSD after trauma. Lastly, we conducted a mediation analysis on the effect of ND severity on PTSD symptoms.

Results

Individuals with ND (n = 1514) were more likely to develop PTSD (odds ratio: 1.59; 95% confidence interval: 1.09–2.32; p = .017) compared with individuals without ND (n = 6047). Smokers (regardless of ND status) (n = 2335) compared with nonsmokers (n = 5226) had no significant effect on risk of PTSD (p = .26). Withdrawal was found to be a mediator of the effect of ND severity on PTSD symptoms.

Conclusions

ND, but not smoking status, increases a smoker’s risk of developing PTSD. This provides information that could aid in preventive strategies for individuals with ND who are exposed to trauma.

Implications

This study provides evidence in a national representative sample of adults in the United States that ND may increase one’s risk of developing PTSD after exposure to trauma. It also shows the directionality of the association between smoking and PTSD. Lastly, it demonstrates that withdrawal may be the link to the association between ND and PTSD. We hope that with these findings, preventative strategies are put in place for smokers who are dependent and are exposed to trauma, such that they do not develop PTSD.
Neural mechanisms that promote food consumption following sleep loss and social stress: an fMRI study in adolescent girls with overweight/obesity
Authors: Jensen Chad D , Zaugg Kelsey K , Muncy Nathan M , Allen Whitney D , Blackburn Robyn , Duraccio Kara M , Barnett Kimberly A , Brock Kirwan C , Jarcho Johanna M
Published: November 2021

Study Objectives

Insufficient sleep and social stress are associated with weight gain and obesity development in adolescent girls. Functional magnetic resonance imaging (fMRI) research suggests that altered engagement of emotion-related neural networks may explain overeating when under stress. The purpose of this study is to explore the effects of acute sleep restriction on female adolescents’ neural responding during social evaluative stress and their subsequent eating behavior.

Methods

Forty-two adolescent females (ages 15−18 years) with overweight or obesity completed a social stress induction task in which they were told they would be rated by peers based on their photograph and profile. Participants were randomly assigned to one night of sleep deprivation or 9 h of sleep the night before undergoing fMRI while receiving positive and negative evaluations from their peers. After which, subjects participated in an ad libitum buffet.

Results

Sleep deprived, relative to nondeprived girls had distinct patterns of neural engagement to positive and negative evaluation in anterior, mid, and posterior aspects of midline brain structures. Moreover, a sleep deprivation-by-evaluation valence-by-caloric intake interaction emerged in bilateral dorsal anterior cingulate. Among sleep deprived girls, greater engagement during negative, but not positive, feedback was associated with lower caloric intake. This was not observed for nonsleep deprived girls.

Conclusions

Results suggest an interaction between acute sleep loss and social evaluation that predicts emotion-related neural activation and caloric intake in adolescents. This research helps to elucidate the relationship between sleep loss, social stress, and weight status using a novel health neuroscience model.
Genome Sequence Data of Leptosphaerulina arachidicola, a Causal Agent of Peanut Scorch Spot in China
Authors: Sheng Yu-Ting , Yu Xiao-Li , Mao Ting-Ting , Zhang Juan , Guo Xiao-Tong , Song Zhi-Zhong , Zhang Hong-Xia
Published: November 2021

Peanut scorch spot caused by Leptosphaerulina arachidicola is one of the most severe leaf diseases of peanut that causes significant yield loss. Here, we report the first high-quality genome sequence of L. arachidicola JB313 isolated from an infected peanut leaf in China. The genome size is 47.66 Mb, consisting of 65 scaffolds (N50 length = 1.58 Mb) with a G+C content of 49.05%. The information in this report will provide a reference genome for future studies on the peanut scorch spot pathogen in peanut.
Enhanced cytotoxic activity of beta carotene conjugated liposomes towards breast cancer cell line: comparative studies with cyclophosphamide
Authors: Mahrous Gina R. , Elkholy Nourhan S. , Safwat Gehan , Shafaa Medhat W.
Published: November 2021

This work aims to evaluate cyclophosphamide (Cyclo) cytotoxic efficacy combined with liposomes in the presence or absence of beta carotene (beta) by detecting the effects of these compounds on the breast cancer cell line (MCF-7) DNA damage. The IC50 value for beta in cytotoxic assay with MCF-7 treated cells was 21.15 μg/ml, while with liposomal beta (LipoBeta) being 121 μg/ml. The free Cyclo IC50 value was 719.86 μg/ml, its liposomal form (LipoCyclo) was 172 μg/ml. The results indicated that in contrast with Cyclo and control values, all comet assay parameters for the LipoBeta were significantly increased (P < 0.05). In MCF-7 cells treated with beta, the findings show a higher intensity of comet tail than those treated with LipoBeta. The presence of several double-strand breaks suggests this high intensity relative to the head. The molecular combination between Cyclo and liposomes in the presence or absence of beta was characterized. Dynamic light scattering measurements confirmed the mono-dispersity of all samples. The incorporation of Cyclo or beta into liposomes exhibited a slight shift to higher temperature compared to the main peak of empty liposomes that exists at 101.5°C which creates a conformational disorder within the phospholipids. The FTIR study showed structural alterations in vesicles after liposome encapsulation.
Sarcoidosis Induced by Atezolizumab Presenting With Xanthelasma Infiltration
Authors: Marcoval Joaquim , Moreno-Vílchez Carlos , Llobera-Ris Claudia , Torrecilla-Vall-Llossera Clara , Penín Rosa M.
Published: November 2021

Sarcoidosis induced by anti-PD1 or anti-PDL1 agents such as atezolizumab has recently been reported. It has been suggested that the predilection of sarcoidosis to affect scars is due to the presence of antigens or foreign bodies that can serve as a stimulus for granuloma formation. However, to the best of our knowledge, sarcoidosis-specific skin lesions have not to date been reported involving xanthelasma. We report a patient who developed specific lesions of sarcoidosis infiltrating some xanthelasmata 6 months after starting treatment with atezolizumab. A 69-year-old woman was referred to the dermatology department for infiltration of xanthelasmata. The patient was being treated with atezolizumab for metastatic uterine carcinosarcoma. Cutaneous biopsy from an infiltrated xanthelasma and from still yellow, no infiltrated xanthelasma showed differing proportions of foamy histiocytes and sarcoid granulomas. On physical examination, erythemato-marronaceous papules clustered on both knees, and not previously detected by the patient, were observed. The biopsy showed sarcoid dermal granulomas with foreign bodies. A chest computerized tomography scan was consistent with intrathoracic involvement of sarcoidosis. Endobronchial ultrasound-guided transbronchial needle aspiration of a mediastinal lymphadenopathy showed epithelioid cell granulomas. Histopathologically, the foamy histiocytes of xanthelasma seem to be replaced by or evolve to epithelioid cells to form sarcoid granulomas. The possible pathogenic mechanism is discussed. Dermatologists and dermatopathologists should bear in mind that sarcoidosis can present as infiltration of pre-existing xanthelasmata.
Reproducible Histopathologic Features in Cases of Basal Cell Carcinoma With Neuroendocrine Expression: A Clinicopathologic Study of 24 Cases With a Potential Diagnostic Pitfall
Authors: Plaza Jose A. , Pootrakul Llana , Raghavan Shyam S. , Sangueza Martin , Gru Alejandro A.
Published: November 2021

Basal cell carcinomas (BCCs) are common malignancies that usually show clear histomorphologic features, but in certain instances, it can display different patterns of differentiation leading to potential diagnostic confusion. BCCs with neuroendocrine differentiation/expression have been mentioned only briefly in the literature. In this study, we present cases of BCCs with neuroendocrine differentiation/expression that demonstrate reproducible histopathological features. Twenty-four cases were included in the study. All tumors showed conventional histopathologic features that are seen in BCCs, but in addition, all the tumors showed large, hyperchromatic, pleomorphic, mononuclear, and multinucleate cells with intracytoplasmic inclusions and intranuclear cytoplasmic invaginations, with rare cases showing stippled nuclei (salt-and-pepper appearance). These histologic features were somewhat concerning for a neuroendocrine carcinoma; thus, immunohistochemistry studies were performed in all cases at the time of diagnosis. By immunohistochemistry, all tumors showed expression of neuroendocrine markers. CD56 was expressed in all cases 24/24, chromogranin was positive in 17/24 cases, and synaptophysin 8/24 was positive in cases. This study confirms a subset of histopathologic features that are present in cases of BCC that are associated with neuroendocrine expression that can potentially be interpreted differently and can create a diagnostic pitfall. Neuroendocrine expression in BCCs is yet uncertain, and further studies are required to fully understand this phenomenon. To avoid diagnostic pitfalls, dermatopathologists must be aware of these unusual histopathologic features and aberrant immunostaining in such tumors; hence, it is advised to perform a thorough histologic inspection.
Sarcomatoid Dedifferentiated Melanoma: The Diagnostic Role of Next-Generation Sequencing
Authors: Valiga Alexander A. , Fuller Collin G. , Doyle Jessica A. , Lee Jason B.
Published: November 2021

Sarcomatoid dedifferentiated melanoma (SDDM) represents a diagnostic challenge as this cutaneous spindle cell melanoma lacks expression of classic melanocytic markers including S100, SOX10, Melan-A, HMB45, and MITF. The expression of the emerging melanoma marker preferentially expressed antigen in melanoma (PRAME) in SDDM is largely unknown. In this article, a case of SDDM arising in association with a nodular melanoma is highlighted. A 65-year-old man presented with a several week history of an ulcerated lesion on the right medial knee. A shave biopsy of the lesion revealed a biphasic neoplasm, which consisted of a centrally located poorly differentiated spindle cell component and an adjacent nodular component consisting of atypical melanocytes arranged in nests and fascicles. While the nodular component stained for S100, SOX10, and Melan-A, the spindle cell component failed to stain for these conventional melanocytic markers, only staining diffusely for CD10 and faintly for CD68. Both components stained for PRAME diffusely albeit less intensely within the spindle cell component. Next-generation DNA sequencing assay of the microdissected biphasic components revealed a shared mutation of NRAS. The results of the PRAME immunohistochemical stain and next-generation DNA sequencing assay facilitated in establishing the diagnosis of SDDM in association with nodular melanoma.
Therapeutic Drug Monitoring of Antibiotic Drugs: The Role of the Clinical Laboratory
Authors: Shipkova Maria , Jamoussi Hedi
Published: November 2021

Background:

Therapeutic drug monitoring (TDM) of anti-infective drugs is an increasingly complex field, given that in addition to the patient and drug as 2 usual determinants, its success is driven by the pathogen. Pharmacodynamics is related both to the patient (toxicity) and bacterium (efficacy or antibiotic susceptibility). The specifics of TDM of antimicrobial drugs stress the need for multidisciplinary knowledge and expertise, as in any other field. The role and the responsibility of the laboratory in this interplay are both central and multifaceted. This narrative review highlights the role of the clinical laboratory in the TDM process.

Methods:

A literature search was conducted in PubMed and Google Scholar, focusing on the past 5 years (studies published since 2016) to limit redundancy with previously published review articles. Furthermore, the references cited in identified publications of interest were screened for additional relevant studies and articles.

Results:

The authors addressed microbiological methods to determine antibiotic susceptibility, immunochemical and chromatographic methods to measure drug concentrations (primarily in blood samples), and endogenous clinical laboratory biomarkers to monitor treatment efficacy and toxicity. The advantages and disadvantages of these methods are critically discussed, along with existing gaps and future perspectives on strategies to provide clinicians with as reliable and useful results as possible.

Conclusions:

Although interest in the field has been the driver for certain progress in analytical technology and quality in recent years, laboratory professionals and commercial providers persistently encounter numerous unresolved challenges. The main tasks that need tackling include broadly and continuously available, easily operated, and cost-effective tests that offer short turnaround times, combined with reliable and easy-to-interpret results. Various fields of research are currently addressing these features.
Postoperative Candida Infection following Complex Periocular Reconstruction
Authors: Wallis Luke S. , Stull Carolyn M. , Rakita Uros , Grushchak Solomiya , Ahmad Amjad Z. , Krunic Aleksandar L.
Published: November 2021

Postoperative candida infection is a rarely reported complication in cutaneous surgery, although it may develop more often in particular clinical settings. We present a 59-year-old woman with a well-controlled human immunodeficiency virus infection. She developed a bright red eruption with satellite pustules 2 weeks after excision of recurrent lentigo maligna melanoma of the left lower eyelid and periocular region. Due to defect size and complexity of the reconstruction (glabellar transposition flap, Hughes flap, composite graft from upper contralateral eyelid, and full-thickness skin graft from ipsilateral retroauricular region), she was placed on prophylactic oral amoxicillin-clavulanic acid and topical bacitracin and polymyxin. Immediate postoperative course was unremarkable, and sutures were removed after 7 days. Three days later, she developed bright red erythema and pustules within the surgical site and complained of burning. Empirically she was switched to topical gentamicin and oral ciprofloxacin, and later to linezolid, due to inadequate response. Wound culture grew Candida albicans sensitive to fluconazole and voriconazole. After oral fluconazole and topical clotrimazole initiation, the patient rapidly improved. The graft remained viable and apart from small partial dehiscence on the cheek, the healing was unremarkable. Apart from the case presentation, we also discuss different factors associated with postoperative candida infection, including immunocompromised status, surgical procedure location, and postoperative antibiotic use. Early recognition and treatment of postoperative candida infections are crucial to prevent delayed healing and associated morbidity.
The Use of a Neurotized Arterio-venous Flow-through Flap for Concurrent Pulp Revascularization and Reconstruction
Authors: Khajuria Ankur , Sethu Arun , Kannan Ruben Y.
Published: November 2021

Digital fingertip soft tissue defects requiring both reconstruction and revascularization pose challenges to the reconstructive surgeon. Traditional options, including terminalization, vein graft and cross-finger flap, and free flow-through flaps, maybe unsuitable or unavailable, with potential for significant donor site morbidity. Venous free flaps rely on venous circulation alone, with no sacrifice of an artery. We present a unique case of a self-employed tradesman with Raynaud’s disease, with four-finger injury, and three-finger ischemia for whom we performed a neurotized arterialized venous flow-through flap to revascularize and reconstruct a pulp defect (with a concomitant vessel gap of 2 cm). After allowing for a period of intrinsic delay, the neurotized arterialized venous flow-through flap was inset after 10 days. The flap survived and the patient began to return to his activities within a month of the injury.
Higher Prevalence of Capsular Contracture with Second-side Use of Breast Implant Insertion Funnels
Authors: Bresnick Stephen D.
Published: November 2021

Background:

Breast implant insertion funnels have become popular adjuncts to breast implant surgery to reduce access incision length and contact of the implant with the skin of the breast. Although labeled as single-use devices, due to cost considerations, many surgeons use a new breast implant insertion funnel with each patient rather than each breast. The purpose of this study was to evaluate the prevalence of capsular contracture of the first augmentation side and compare it to the second side utilizing one insertion funnel per patient.

Methods:

Patients undergoing silicone breast augmentation or silicone augmentation mastopexy with smooth surface silicone implant and utilizing a breast implant insertion funnel were studied. Six hundred consecutive patients (1200 breasts) meeting the study criteria were evaluated. Memory Gel silicone breast implants were utilized for each patient and only patients undergoing augmentation with the same implant size were studied. Patients underwent augmentation with either inframammary or periareolar incisions.

Results:

A total of 27 capsular contractures were noted, a rate of 2.25%. The rate of capsular contracture was significantly higher with the second-side use of insertion funnels (P = 0.0179). Of the capsular contractures noted, 25.9% occurred on the first side, whereas 74.1% occurred on the second side. Capsular contracture rates were higher on the second side for both access incision locations. Capsular contracture prevalence increased with reuse of the same insertion funnel for the same patient.

Conclusion:

Based on these findings, surgeons should consider utilizing implant insertion devices as single-use, to minimize the capsular contracture risk.
Nutrition Intervention in Cardiac Rehabilitation
Authors: Lara-Breitinger Kyla , Lynch Michael , Kopecky Stephen
Published: November 2021

Objective:

Despite guideline consensus that quality of nutrition affects most modifiable cardiovascular disease risk factors, the implementation of dietary interventions varies considerably in cardiac rehabilitation (CR) programs. The purpose of this review is to highlight the current existing literature and provide recommendations on best practices for nutrition interventions and future research that support secondary prevention outcomes.

Review Methods:

The review examines original investigations, systematic reviews, and guidelines regarding nutrition intervention in CR.

Nutrition intervention in CR plays an integral role in the success of patients; however, the literature is limited and standardization of practice is in its infancy. The role of a qualified registered dietician nutritionist, standardization of dietary assessments, individualized and intensive nutrition interventions, and application of specific behavior change techniques are central components in improving diet in CR. This review provides an overview of the evidence-based cardioprotective diets, nutritional interventions and behavioral strategies in CR, and explores areas for best practices and opportunities for innovation in the delivery of nutrition intervention in CR.
Peripheral GABAA receptor signaling contributes to visceral hypersensitivity in a mouse model of colitis
Authors: Loeza-Alcocer Emanuel , Gold Michael S.
Published: November 2021

Pain is a common and debilitating symptom of inflammatory bowel disease (IBD). Based on evidence that peripheral GABAA receptor (GAR) inhibition plays an important role in establishing colonic afferent excitability and nociceptive threshold, we hypothesized that the increase in pain associated with IBD is due to, at least in part, a decrease in peripheral GAR–mediated inhibition. Acute colitis was induced with 5 days of dextran sodium sulfate (DSS, 3%) in the drinking water. Visceral sensitivity was assessed with the visceromotor response (VMR) evoked with balloon distention of the colon in control and DSS-treated mice before and after intracolonic administration of GAR agonist muscimol, the high-affinity GAR preferring agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-3-ol (THIP), the GAR positive allosteric modulator diazepam, or the GAR antagonists gabazine and bicuculline. Low concentrations of muscimol or THIP increased the VMR in DSS-treated mice but not in control mice. However, high concentrations of muscimol decreased the VMR in both control and DSS-treated mice. Diazepam decreased the VMR in both DSS-treated and control mice. By contrast, at a concentration of gabazine that blocks only low-affinity GAR, there was no effect on the VMR in either DSS-treated or control mice, but at concentrations of the antagonist that block low-affinity and high-affinity GAR, the VMR was increased in control mice and decreased in DSS-treated mice. Furthermore, bicuculline increased the VMR in control mice but decreased it in DSS-treated mice. These data suggest that activating of low-affinity GAR or blocking high-affinity GAR may be effective therapeutic strategies for the management of pain in IBD.
Term Singleton Vertex Cesarean Birth Rates in the Military Health System
Authors: Farrell Maureen E. , Lutgendorf Monica A.
Published: November 2021

Cesarean births have increased in the United States, accounting for approximately one-third of all births. There is concern that cesarean birth is overused, due to the wide variation in rates geographically and at different institutions within the same region. Despite the rising rate, there has not been an improvement in maternal or neonatal outcomes. Consequently, the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine published recommendations aimed at the safe prevention of primary cesarean births in 2014. The purpose of this project was to identify the term singleton vertex cesarean birth rates in the Military Health System's hospitals; to compare the Military Health System's rate of term singleton vertex cesarean birth to published benchmarks; and to compare term singleton vertex cesarean birth rates over time and among facilities within the Military Health System to determine whether variation existed. This was a retrospective review of aggregate data reported by the National Perinatal Information Center. Data were analyzed over 9 years at 2-year intervals from 2011 through 2019 inclusively. The Military Health System exceeded national benchmarks for term singleton vertex cesarean birth rates and had less variation over time and among facilities.
Do Single-Family Rooms Increase Parental Presence, Involvement, and Maternal Well-Being in Neonatal Intensive Care?
Authors: Campbell-Yeo Marsha , Kim Theresa , Disher Tim , Richardson Brianna , Dol Justine , Bishop Tanya , Delahunty-Pike Alannah , Dorling Jon , Glover Megan , Inglis Darlene , Johnson Teresa , Macmillan Doug , Mcgrath Patrick , Monaghan Joelle , Orovec Adele , Simpson David C. , Skinner Natasha , Whitehead Leah , Wozney Lori
Published: November 2021

Objectives of this study were to determine whether single-family room (SFR) design enhances parental presence, involvement, and maternal well-being during neonatal intensive care hospitalization. An observational cohort including mothers of infants was randomly assigned to receive care in a tertiary-level open-bay (OB) (n = 35) or SFR (n = 36). Mothers were asked to complete daily diaries documenting parental presence, involvement in care, and questionnaires examining maternal well-being. Mother and father mean presence (standard deviation) was significantly higher in the SFR—17.4 (5.2) and 13.6 (6.8)—compared to OB—11.9 (6.3) and 4.6 (3.7) hours/day. Total time spent in care activities did not differ for mothers, except SFR mothers spent more time expressing breast milk (EBM). SFR fathers had greater involvement with care activities. There were no other significant differences. The SFR was associated with greater maternal presence, but not greater involvement in care activities except for EBM, nor improved maternal well-being. The SFR appears to have greater impact on fathers' involvement in care and comforting activities, although the amount of time involved remained quite low compared with mothers. Further studies examining ways to enhance parental involvement in the neonatal intensive care unit are warranted.
Using Social Media to Disseminate Effective Pain Treatments for Newborns During Needle-Related Painful Procedures in China
Authors: Hu Jiale , Xue Feng , Zhou Yiyan , Liu Yuxiao , Li Qingge , Deng Jun , Harrison Denise
Published: November 2021

Social media has become a powerful approach to disseminating evidence to knowledge users. The BSweet2Babies video was developed in multiple languages showing the effectiveness of sweet solutions, skin-to-skin care, and breastfeeding during newborn painful procedures. This study aimed to disseminate the BSweet2Babies video in Chinese through social media platform of WeChat in China; evaluate the reach, acceptability, and recommendation of the video; and assess viewers' previous knowledge and experience of using the 3 strategies and intention to use these strategies in the future. Multiple dissemination strategies were used to maximize views for a 6-month dissemination period. The video received 19 812 views, 4306 “thumbs,” and 671 participants completed surveys. Of the survey respondents, 393 were parents. Most respondents did not know these strategies and did not use or help parents use any of them. More healthcare professionals than parents intended to use or advocate for sweet solutions and breastfeeding. More healthcare professionals rated that the 3 strategies were easy to apply in real-life situations, but more parents evaluated that the length of the video was too long. Social media in China can be a promising approach to disseminating evidence on neonatal procedural pain treatments to healthcare professionals and the public.
Phosphatases of regenerating liver are key regulators of metabolism in cancer cells – role of Serine/Glycine metabolism
Authors: Abdollahi Pegah , Vandsemb Esten N. , Børset Magne
Published: November 2021

Purpose of review

Phosphatases of regenerating liver (PRL) are dual-specificity phosphatases and comprise three members, PRL-1, -2 and -3. Despite the importance of PRLs as oncoproteins, there is no consensus function for this family of phosphatases. In the current review paper, we summarize recent findings on the role of PRLs in metabolic regulation.

Recent findings

Reprogramming of cellular metabolism is a cancer hallmark. Glucose is the major source of energy in cells. Glucose metabolism occurs through the glycolysis and can continue through the pathways such as serine synthesis pathway or the tricarboxylic acid cycle (TCA). Magnesium (Mg2+), the second most abundant cation in cells, plays an essential role in energy production by acting as a cofactor for most enzymes involved in glycolysis and in TCA. Recent findings have shown that the PRL family has a role in metabolic reprogramming mediated by (1) Mg2+ homeostasis, (2) shifting the energy source preference to glucose consumption and fueling serine/glycine pathway and (3) regulating PI3 kinase/Mammalian target of rapamycin complex. Both the phosphatase and nonphosphatase activity of PRLs appear to be important for its oncogenic role.

The PRL family contributes to the metabolic plasticity of cancer cells and, thereby, allows cancer cells to meet the high metabolic demands required for cell proliferation.
Novel approach to unpleasant symptom clusters surrounding pruritus in patients with chronic kidney disease and on dialysis therapy
Authors: Ahdoot Rebecca S. , Kalantar-Zadeh Kamyar , Burton James O. , Lockwood Mark B.
Published: November 2021

Purpose of review

Chronic kidney disease-associated-pruritus (CKD-aP) is a common symptom in patients with end-stage kidney disease (ESKD) undergoing dialysis. CKD-aP typically occurs alongside other debilitating symptoms and may comprise so-called ‘symptom clusters’ which have synergistic effects that adversely impact patient health-related quality of life (HRQoL). Importantly, symptoms in a cluster may share a common biological mechanism. Here we review the clinical impact of CKD-aP and its association with other symptoms reported by dialysis patients. The clinical benefits of treating pruritus and its potential impact on other symptoms are also addressed.

Recent findings

Studies have shown CKD-aP significantly impairs HRQoL in patients with ESKD undergoing dialysis and is associated with adverse clinical outcomes, including increased risk of infections, hospitalizations, and mortality. Despite these negative effects, CKD-aP remains underrecognized and undertreated in clinical practice. CKD-aP is frequently associated with other symptoms, including disturbed sleep/poor sleep quality, anxiety, depression, and pain. Clinical studies of antipruritic therapies show that reduction of itch intensity may also alleviate other associated symptoms, such as poor sleep quality.

CKD-aP and its associated symptoms are inadequately managed in clinical practice. Greater understanding and awareness of CKD-aP and its surrounding symptom clusters in dialysis patients may improve their overall symptom management and HRQoL.
NSs of the mildly virulent sandfly fever Sicilian virus is unable to inhibit interferon signaling and upregulation of interferon-stimulated genes
Authors: Wuerth Jennifer Deborah , Weber Friedemann
Published: November 2021

Phleboviruses (order Bunyavirales, family Phenuiviridae) are globally emerging arboviruses with a wide spectrum of virulence. Sandfly fever Sicilian virus (SFSV) is one of the most ubiquitous members of the genus Phlebovirus and associated with a self-limited, incapacitating febrile disease in travellers and military troops. The phleboviral NSs protein is an established virulence factor, acting as antagonist of the antiviral interferon (IFN) system. Consistently, we previously reported that SFSV NSs targets the induction of IFN mRNA synthesis by specifically binding to the DNA-binding domain of the IFN transcription factor IRF3. Here, we further characterized the effect of SFSV and its NSs towards IFN induction, and evaluated its potential to affect the downstream IFN-stimulated signalling and the subsequent transactivation of antiviral interferon-stimulated genes (ISGs). We found that SFSV dampened, but did not entirely abolish type I and type III IFN induction. Furthermore, SFSV NSs did not affect IFN signalling, resulting in substantial ISG expression in infected cells. Hence, although SFSV targets IRF3 to reduce IFN induction, it is not capable of entirely disarming the IFN system in the presence of high basal IRF3 and/or IRF7 levels, and we speculate that this significantly contributes to its low level of virulence.
The influence of unmeasured confounding on the MR Steiger approach
Authors: Lutz Sharon M. , Voorhies Kirsten , Wu Ann Chen , Hokanson John , Vansteelandt Stijn , Lange Christoph
Published: November 2021

The Mendelian Randomization (MR) Steiger approach is used to determine the direction of a possible causal effect between two phenotypes [1]. For two phenotypes, denoted phenotype 1 and 2, the MR Steiger approach is composed of two parts: (1) MR is performed for a set of single nucleotide polymorphisms (SNPs) that serve as instrumental variables for phenotype 1 and (2) the difference of two correlations, the correlation between the SNPs and phenotype 1 and the correlation between the SNPs and phenotype 2, is calculated. These two parts are then used to determine the direction of a possible causal effect between the two phenotypes. The original MR Steiger paper [1] shows that unmeasured confounding of the two phenotypes affects the validity of the MR Steiger approach, but does not elucidate as to how this occurs. In particular, it was argued that if the magnitude of the observational variance explained between the two phenotypes is above 0.2, the MR Steiger method may return the incorrect causal direction due to unmeasured confounding. This may initially seem surprising since unmeasured confounding does not induce spurious associations between the SNP and phenotype 2, as we demonstrate using directed acyclic graphs. In this note, we show that this is because unmeasured confounding may rescale the magnitude of a non-zero association, and thereby distort the comparison of the correlation between the SNP and phenotype 2 and the correlation between the SNP and phenotype 1. We will end with a number of cautionary remarks on the MR Steiger method, which are partly motivated by this and mentioned in the original MR Steiger paper [1].
Effect of plant tissues on DNA quantity and quality of barley (Hordeum vulgare) validating through PCR technique
Authors: Kefelegn Nigussie , Haile Gizachew , Palanivel Hemalatha
Published: November 2021

The use of molecular techniques to deal with plant molecular breeding requires the extraction of genomic DNA in good quantity and quality, which can be influenced by method of extraction and source of DNA (plant species, plant part or tissues). However, this research focuses on plant tissue source and tried to describe the quality and quantity of DNA isolated from different tissues’ of barley crop. CTAB protocol was used for the isolation of DNA and both the quality and quantity of this DNA was validated through gel electrophoresis, Qubit quantification and PCR amplifications. The result showed that DNA could be successfully extracted from all tissues of plants and the yield of DNA obtained was variable ranging from 179ng μl-1in stem to 750ng μl-1in young leave. Band intensity of genomic and PCR amplified DNA was good for DNA isolated from young and matured leave. Faint band was observed in the PCR amplification for DNA isolated from stem but no to unreliable amplification was obtained for seeds and roots, respectively. Thus, for any molecular technique in barley crop research, the best tissue for DNA isolation using modified CTAB, is young or matured leave and alternatively stem can be used as DNA source.
Quantitative model suggests both intrinsic and contextual features contribute to the transcript coding ability determination in cells
Authors: Kang Yu-Jian , Li Jing-Yi , Ke Lan , Jiang Shuai , Yang De-Chang , Hou Mei , Gao Ge
Published: November 2021

Gene transcription and protein translation are two key steps of the “central dogma”. It is still a major challenge to quantitatively deconvolute factors contributing to the coding ability of transcripts in mammals. Here, we propose Ribosome Calculator (RiboCalc) for quantitatively modeling the coding ability of RNAs in human genome. In addition to effectively predicting the experimentally confirmed coding abundance via sequence and transcription features with high accuracy, RiboCalc provides interpretable parameters with biological information. Large-scale analysis further revealed a number of transcripts with a variety of coding ability for distinct types of cells (i.e., context-dependent coding transcripts, CDCTs), suggesting that, contrary to conventional wisdom, a transcript’s coding ability should be modeled as a continuous spectrum with a context-dependent nature.
Association between stroke and psychosis across four nationally representative psychiatric epidemiological studies
Authors: Bell Vaughan , Tamayo-Agudelo William , Revill Grace , Okai David , Poole Norman
Published: November 2021

Background

Both stroke and psychosis are independently associated with high levels of disability. However, psychosis in the context of stroke has been under-researched. To date, there are no general population studies on their joint prevalence and association.

Aims

To estimate the joint prevalence of stroke and psychosis and their statistical association using nationally representative psychiatric epidemiology studies from two high-income countries – United Kingdom and the United States – and two middle-income countries – Chile and Colombia, and, subsequently, in a combined countries dataset.

Methods

Prevalences were calculated with 95% confidence intervals. Statistical association between stroke and psychosis, and stroke and psychotic symptoms, was tested using regression models. Overall estimates were calculated using an individual participant level meta-analysis on the combined countries dataset. The analysis is available online as a computational notebook.

Results

The overall prevalence of probable psychosis in stroke was 3.81% [95% CIs 2.34 - 5.82] and stroke in probable psychosis was at 3.15% [95% CIs 1.94 - 4.83]. The adjusted association between stroke and probable psychosis was OR = 3.32 [95% CIs 2.05 - 5.38]. On the individual symptom level, paranoia, hallucinated voices, and thought passivity delusion were associated with stroke in the unadjusted and adjusted analyses.

Conclusions

Rates of association between psychosis and stroke suggest there is likely a high clinical need group who are under-researched and may be poorly served by existing services.
Chronic elevation of serum S100B but not neurofilament-light due to frequent choking/strangulation during sex in young adult women
Authors: Alexander Isabella L. , Huibregtse Megan E. , Fu Tsung-Chieh , Klemsz Lillian M. , Fortenberry J. Dennis , Herbenick Debby , Kawata Keisuke
Published: November 2021

Being choked/strangled during a partnered sex is an emerging sexual behavior, particularly prevalent among adolescent and young adult women, but the neurobiological impact of choking remains unknown. This case-control study aimed to test whether frequent choking during sex influences neurological health in young adult women, as assessed by serum levels of S100B and neurofilament-light (NfL). Participants who reported being choking ≥4 times during sex in the past 30 days were enrolled into a choking group, whereas those without were assigned to a control group. Serum samples were collected and assessed for S100B and NfL levels. Demographic questionnaires as well as alcohol use, depression, and anxiety scales were also obtained. Fifty-seven participants were enrolled initially. Due to voluntary withdrawal, phlebotomy difficulties, and scheduling conflicts, the final sample size of 32 subjects (choking n=15; control n=17) was eligible for analysis. After adjusting for a significant covariate (race), the choking group exhibited significantly elevated levels of S100B relative to controls (B=13.96 pg/mL, SE=5.41, p=0.016) but no significant group differences in NfL levels. A follow-up receiver operating characteristic analysis revealed that serum levels of S100B had very good accuracy for distinguishing between the choking and control groups [AUC=0.811, 95%CI (0.651, 0.971), p=0.0033]. Our S100B provide evidence of recurring astrocyte activation due to frequent choking while the NfL data indicate that axonal microstructural integrity may be resilient to these transient hypoxic stressors. Further clinical investigation is needed to clarify the acute and chronic neurological consequences of being choked during sex using a multimodal neurologic assessment.
Drag-and-drop genome insertion without DNA cleavage with CRISPR-directed integrases
Authors: Ioannidi Eleonora I. , Yarnall Matthew T. N. , Schmitt-Ulms Cian , Krajeski Rohan N. , Lim Justin , Villiger Lukas , Zhou Wenyuan , Jiang Kaiyi , Roberts Nathaniel , Zhang Liyang , Vakulskas Christopher A. , Walker John A. , Kadina Anastasia P. , Zepeda Adrianna E. , Holden Kevin , Gootenberg Jonathan S. , Abudayyeh Omar O.
Published: November 2021

Programmable and multiplexed genome integration of large, diverse DNA cargo independent of DNA repair remains an unsolved challenge of genome editing. Current gene integration approaches require double-strand breaks that evoke DNA damage responses and rely on repair pathways that are inactive in terminally differentiated cells. Furthermore, CRISPR-based approaches that bypass double stranded breaks, such as Prime editing, are limited to modification or insertion of short sequences. We present Programmable Addition via Site-specific Targeting Elements, or PASTE, which achieves efficient and versatile gene integration at diverse loci by directing insertion with a CRISPR-Cas9 nickase fused to both a reverse transcriptase and serine integrase. Without generating double stranded breaks, we demonstrate integration of sequences as large as ∼36 kb with rates between 10-50% at multiple genomic loci across three human cell lines, primary T cells, and quiescent non-dividing primary human hepatocytes. To further improve PASTE, we discover thousands of novel serine integrases and cognate attachment sites from metagenomes and engineer active orthologs for high-efficiency integration using PASTE. We apply PASTE to fluorescent tagging of proteins, integration of therapeutically relevant genes, and production and secretion of transgenes. Leveraging the orthogonality of serine integrases, we engineer PASTE for multiplexed gene integration, simultaneously integrating three different genes at three genomic loci. PASTE has editing efficiencies comparable to or better than those of homology directed repair or non-homologous end joining based integration, with activity in non-dividing cells and fewer detectable off-target events. For therapeutic applications, PASTE can be delivered as mRNA with synthetically modified guides to programmably direct insertion of DNA templates carried by AAV or adenoviral vectors. PASTE expands the capabilities of genome editing via drag-and-drop gene integration, offering a platform with wide applicability for research, cell engineering, and gene therapy.

One Sentence Summary

A new technology combining CRISPR-mediated genome editing and site-specific integrases enables efficient programmable gene integration at any targeted genomic locus without double-strand DNA breaks, leading to broad applications in basic science research, cell engineering, and gene therapy.
A new analytic solution of complex Langevin differential equations
Authors: Ibrahim Rabha W.
Published: November 2021

Purpose

In this study, the authors introduce a solvability of special type of Langevin differential equations (LDEs) in virtue of geometric function theory. The analytic solutions of the LDEs are considered by utilizing the Caratheodory functions joining the subordination concept. A class of Caratheodory functions involving special functions gives the upper bound solution.

Design/methodology/approach

The methodology is based on the geometric function theory.

Findings

The authors present a new analytic function for a class of complex LDEs.

Originality/value

The authors introduced a new class of complex differential equation, presented a new technique to indicate the analytic solution and used some special functions.
Stock liquidity and stock return: an asymmetric impact of institutional ownership approach
Authors: Daryaei Abbas Ali , Fattahi Yasin
Published: November 2021

Purpose

This study is primarily aimed at investigating the asymmetric impact of institutional ownership on the relationship between stock liquidity and stock return. It was conducted by testing the hypotheses regarding efficient monitoring and adverse selection from Tehran Stock Exchange (TSE).

Design/methodology/approach

Using a panel smooth transition regression model and selecting 183 firms for the period from 2009 to 2019 from TSE, this study examined the data to explore the asymmetric impact of institutional ownership on the relationship between stock liquidity and stock return.

Findings

The results show a positive impact by institutional ownership on the relationship between stock liquidity and stock return in the first regime (threshold level 39%), whereas in the second regime, there is a negative impact by institutional ownership on the relationship between stock liquidity and stock return. Furthermore, the firms were divided into two groups based on the market value. The first group includes those with a market share less than the mean total market value of the sample. The second group includes firms with a market share higher than the mean total market value of the sample (large firms). The results illustrate that the threshold level is 32% and 44% for the first and second groups, respectively.

Originality/value

The findings of this study suggest that institutional ownership theories require closer inquiry.
Challenges of e-government implementation in health sector: a step toward validating a conceptual framework
Authors: Khan Abdul Zahid , Mahmood Faisal , Bokhari Rahat Hussain , Mushtaq Rabia , Abbas Raza
Published: November 2021

Purpose

The importance of e-government projects has been realized in the developed as well as in the developing countries of the world. The successful implementation of e-government projects is a challenging task. Public sector organizations are facing different sorts of challenges while executing e-government initiatives. The purpose of this paper is to explore issues/challenges related to e-government project implementation.

Design/methodology/approach

A systematic literature review (SLR) was conducted to understand the challenges of the e-government project, as mentioned in past research. The findings of this SLR helped in developing a proposed framework for e-government challenges. The proposed framework encompasses challenges and issues related to four main aspects such as technological, organizational, project management and enabling environment. These aspects need to be further explained for their remedial measures. For this purpose, an exploratory case study was conducted. The unit of analysis was one of the e-government projects of the ministry of IT. The interviews of the senior and middle management involved in the implementation of this project were conducted and transcribed.

Findings

The case study findings endorse a framework proposed. The findings of this research reflect the importance of creating a shared vision, adequate funding and good project management practices as an essential aspect of e-government implementation. Further, the importance of user-related issues such as involvement, capacity building and technical skills was also found critical in successfully executing and sustaining such initiatives in the organization. Further study findings provide necessary guidance for the senior management, which may help to develop effective strategies for the e-government projects in the organization.

Originality/value

The current study focused on developing a better understanding of the challenges commonly faced by organizations during e-government adoption and implementation related to organizational, project management, enabling environment and technological aspects.