bluuebunny/crossref_metadata_2025 huggingface dataset:
Animation supported communication on intensive care; a service improvement initiative
Authors: Wachtl Marta , Ledesma Frances , Malcolm Hannah , Toal Connor , Kavanagh Charlotte , Hadley Julia , Pennington James , Shepherd Stephen , Wald David S
Published: July 2021

Objective

COVID-19 has created unique challenges for families of patients admitted to intensive care units. Restricted visiting, language barriers and time constraints have limited communication, resulting in a lack of understanding and anxiety. We introduced digital animations to support communication and assessed the impact on families of patients admitted to intensive care.

Methods

Multi-language animations explaining mechanical ventilation, ( www.explainmyprocedure.com/icu ) were introduced at two London intensive care units during the COVID-19 pandemic. Web-links were sent by email. Reported understanding of the treatment, its benefits, risks and alternatives was assessed among family contacts of 71 consecutive patients admitted to intensive care; 39 before the animations were introduced (no animation group) and 32 afterwards (animation group). Reported understanding in the two groups was assessed by telephone questionnaire and compared.

Results

Following introduction, all relatives reported they had watched the animation. The proportions who reported complete understanding of mechanical ventilation, its benefits, risks and alternatives, in the no animation group (n = 39) were, respectively, 15%, 28%, 0% and 3% and in the animation group (n = 32), 94%, 97%, 84% and 66% (p < 0.0001 for all comparisons).

Conclusion

Family use of online multi-language animations explaining mechanical ventilation is feasible, acceptable and associated with substantial improvement in understanding. The approach is not limited to mechanical ventilation, or to use in a pandemic, and has the potential to be applied to a wide range of treatment and recovery pathways on intensive care.
Horror Films and Grief
Authors: Millar Becky , Lee Jonny
Published: July 2021

Many of the most popular and critically acclaimed horror films feature grief as a central theme. This article argues that horror films are especially suited to portraying and communicating the phenomenology of grief. We explore two overlapping claims. First, horror is well suited to represent the experience of grief, in particular because the disruptive effects of horror “monsters” on protagonists mirror the core experience of disruption that accompanies bereavement. Second, horror offers ways in which the experience of grief can be contained and regulated and, in doing so, may offer psychological benefits for the bereaved. While our focus will be squarely on film, much of what we say applies to other media.
Legal Frameworks: A Starting Point for Strengthening Medicolegal Death Investigation Systems and Improving Cause and Manner of Death Statistics in Civil Registration and Vital Statistics Systems
Authors: Joos Olga , Mrkic Srdjan , Sferrazza Lynn
Published: July 2021

Medicolegal death investigation systems, which generally fall within one of three types—medical examiner, coroner, or law-enforcement-led systems—investigate deaths that are unnatural or suspicious. The current quality of cause of death statistics on deaths investigated within medicolegal death investigation systems globally limits effective public health response. A starting point to strengthening global medicolegal death investigation systems and improving the quality of cause and manner of death reported to civil registration systems is through a strong legal framework. Two resources, the United Nations Statistics Division Guidelines on the Legislative Framework for Civil Registration, Vital Statistics and Identity Management and the Global Health Advocacy Incubator Legal and Regulatory Toolkit for Civil Registration, Vital Statistics and Identity Management, present recommendations and provide guidance to country stakeholders in reviewing and revising their medicolegal death investigation legal frameworks. Physician determination of cause and manner of death, defined criteria for case referral to the medicolegal death investigation system, an amendment process, and investigation collaboration are four core considerations for medicolegal death investigation system legal frameworks. A strong medicolegal death investigation legal framework is a necessary starting point, but it is not sufficient for ensuring the timely, accurate, and complete reporting of cause and manner of death in national vital statistics.
Network Pharmacology-Based Investigation on the Anti-Osteoporosis Mechanism of Astragaloside IV
Authors: Ou Li , Kang Wenqian , Zhang Jiahao , Wei Peifeng , Li Min , Gao Feng , Dong Taiwei
Published: July 2021

Astragaloside IV is the main active ingredient of Astragalus membranaceus. Studies have found that it can promote the proliferation of osteoblasts and can antagonize the apoptosis of mouse osteoblasts induced by hydrogen peroxide, but its molecular mechanism for the treatment of osteoporosis is still not clear. First, we used 3 online platforms: CTD, PharmMapper and SwissTargetPrediction to retrieve the targets of Astragaloside IV, and collected osteoporosis-related targets. Next, we used Cytoscape 3.7.2 software to construct a visual network diagram of PPI and further screened the key genes of Astragaloside IV in the treatment of osteoporosis using cluster analysis. Finally, after the receptor and ligand were docked, the binding activity was assessed by docking score. We obtained 102 overlapping targets of Astragaloside IV and osteoporosis. According to the node degree value in the PPI network, the top 10 genes were PIK3CA, MAPK1, SRC, STAT3, VEGFA, HSP90AA1, RELA, AKT1, IGF1, EGFR, of which SRC, AKT1, PIK3CA could bind stably to Astragaloside IV. KEGG pathway enrichment results showed that Astragaloside IV treated osteoporosis through 10 main pathways, including PI3K-Akt signaling pathway, FoxO signaling pathway, MAPK pathway, and so on. The classification of these pathways belongs to signal transduction, immune system, development and regeneration and endocrine system. Astragaloside IV is significantly related to several pathways involved in osteoporosis, such as PI3K-Akt, FoxO signaling pathway and MAPK pathway. SRC, AKT1, and PIK3CA can bind stably with Astragaloside IV, and they may be hub genes for the treatment of osteoporosis.
The Display of Medical Information: Content, Format, and Subjective Experience
Authors: Devlin Ann Sloan , Anderson Alaina , Carlson Katie , DiPalo Maggie , Hession-Kunz Sarah , Zou Amy
Published: July 2021

Objectives:

To address a gap in the literature by investigating the subjective experience of participants to the form and content of medical information displayed in a healthcare setting.

Background:

Artwork can enhance the experience of patients, but much less is known about how individuals react to displays of medical information in the form of posters or pamphlets, especially those about unsettling conditions (e.g., skin cancer).

Methods:

In a 2 × 2 × 2 between-subjects design, researchers investigated the content of medical information (skin cancer vs. skin care) that was on display in a simulated exam room, whether the form was a pamphlet or a poster, and reason for the visit (routine annual skin check or evaluating a mole) on measures of subjective experience, including anxiety.

Results:

Viewing material about skin cancer produced greater anxiety and greater arousal than did viewing material about sunscreen, and given the choice of four images (pamphlet and poster for sunscreen, pamphlet and poster for skin cancer), the sunscreen poster was recommended to improve the patient’s experience and lower stress. In terms of display format, posters are judged to provide more visual engagement than are pamphlets.

Conclusions:

Exam rooms should offer multiple opportunities for visual engagement without images that produce anxiety. More research is needed to understand the subjective experience of the patient’s interaction with the content and format of medical information.
Neurocognitive and Neurophysiological Functions Related to ACL Injury: A Framework for Neurocognitive Approaches in Rehabilitation and Return-to-Sports Tests
Authors: Piskin Daghan , Benjaminse Anne , Dimitrakis Panagiotis , Gokeler Alli
Published: July 2021

Context:

Only 55% of the athletes return to competitive sports after an anterior cruciate ligament (ACL) injury. Athletes younger than 25 years who return to sports have a second injury rate of 23%. There may be a mismatch between rehabilitation contents and the demands an athlete faces after returning to sports. Current return-to-sports (RTS) tests utilize closed and predictable motor skills; however, demands on the field are different. Neurocognitive functions are essential to manage dynamic sport situations and may fluctuate after peripheral injuries. Most RTS and rehabilitation paradigms appear to lack this aspect, which might be linked to increased risk of second injury.

Objective:

This systematic and scoping review aims to map existing evidence about neurocognitive and neurophysiological functions in athletes, which could be linked to ACL injury in an integrated fashion and bring an extensive perspective to assessment and rehabilitation approaches.

Data Sources:

PubMed and Cochrane databases were searched to identify relevant studies published between 2005 and 2020 using the keywords ACL, brain, cortical, neuroplasticity, cognitive, cognition, neurocognition, and athletes.

Study Selection:

Studies investigating either neurocognitive or neurophysiological functions in athletes and linking these to ACL injury regardless of their design and technique were included.

Study Design:

Systematic review.

Level of Evidence:

Level 3.

Data Extraction:

The demographic, temporal, neurological, and behavioral data revealing possible injury-related aspects were extracted and summarized.

Results:

A total of 16 studies were included in this review. Deficits in different neurocognitive domains and changes in neurophysiological functions could be a predisposing risk factor for, or a consequence caused by, ACL injuries.

Conclusion:

Clinicians should view ACL injuries not only as a musculoskeletal but also as a neural lesion with neurocognitive and neurophysiological aspects. Rehabilitation and RTS paradigms should consider these changes for assessment and interventions after injury.
Subarachnoid hemorrhage from sudden gravitational changes
Authors: Rabinstein Alejandro A , Braksick Sherri A , Wijdicks Eelco FM
Published: July 2021

Diffuse subarachnoid hemorrhage is commonly attributed to the rupture of intracranial aneurysms or other vascular malformations. Non-aneurysmal hemorrhages often have a characteristic pattern or clear mechanism (e.g. trauma) with an often more benign clinical course. We report the case of a diffuse non-aneurysmal subarachnoid hemorrhage due to sudden gravitational changes encountered during complex airflight maneuvers, complicated by hydrocephalus and cerebral vasospasm. This case illustrates a rare phenomenon that may again be encountered in the future with the advent and advancement of civilian spaceflight.
Unprovoked serotonin syndrome-like presentation of SARS-CoV-2 infection: A small case series
Authors: Keith Philip , Saint-Jour Marc , Pusey Frank , Hodges Jeremy , Jalali Farid , Scott L Keith
Published: July 2021

Clinicians and researchers have reported an array of neurological abnormalities in coronavirus disease 2019 (COVID-19), and while serotonin excess has been observed we are unaware of reports of central nervous system serotonin toxicity in COVID-19. We present two cases that resemble serotonin syndrome in COVID-19, but without identifiable inciting medications. A 54-year-old with multiple sclerosis and diabetes mellitus presented with altered mental status. His altered sensorium was attributed to diabetic ketoacidosis, but his condition quickly deteriorated with fever to 105 degrees Fahrenheit, rigidity in all extremities, inducible clonus, and hyperreflexia. He was intubated and was treated for possible meningitis and seizure. Neurologic workup was negative for acute pathology. Despite acetaminophen, his core temperature remained elevated to 105 degrees Fahrenheit. He was treated with external cooling and cyproheptadine and within 48 h, his fever, rigidity, hyperreflexia, and clonus resolved. He was extubated and discharged home on day 14. A 72-year-old with hyperlipidemia was admitted with tremors, 4 days after testing positive for COVID-19. His symptoms rapidly worsened, and he was transferred to the Intensive Care Unit on day 3 in extremis, febrile to 104.4 degrees Fahrenheit, heart rate of 180 beats per minute, and apparent whole body myoclonus. He was intubated and developed fever refractory to acetaminophen requiring external cooling. Extensive neurologic workup was negative. He received cyproheptadine and slowly improved. He was extubated and discharged to rehab on day 11. These cases represent a unique presentation in COVID-19 that must be considered and requires a high index of suspicion.
Liver injury mediated by the UII and its receptor (UT) system is possibly associated with the activation of autophagy-related and apoptosis-resisted pathways of Kupffer cells in acute liver failure
Authors: Zhong Huan , He Yu , Yang Xue , Si Qin-Qin , Xie Pin , Gao De-Yong , Liu Liang-Ming
Published: July 2021

The system of urotensin II (UII) and its receptor (UT) (or: UII/UT system) mediates hepatic immune inflamed injury in acute liver failure (ALF) with autophagy inhibition. However, it is unknown whether the system has an effect on liver autophagy in ALF. In this study, we attempted to explore hepatic autophagy response in ALF through blocking the UII/UT signal. Autophagy-related genes were examined in the liver tissues of lipopolysaccharide (LPS)/d-galactosamine (D-GalN)-induced ALF after pretreatment of UT receptor specific antagonist urantide. And then, the levels of autophagy- and apoptosis-related genes were assayed in LPS-stimulated KCs via urantide pretreatment. We found that the expressions of hepatic autophagy related genes, including Beclin-1, Atg5, Atg7, LC3 and p62 mRNA, and LC3 II and p62 protein, were significantly downregulated in LPS/D-GalN-induced ALF mice; but they were not affected by pretreatment of urantide, a special UT receptor antagonist. To probe inflammatory mechanisms of the UII/UT system, we further investigated the effect of the system on Kupffer cells (KCs), the innate immune cells in liver. We found that urantide pretreatment significantly inhibited production of inflammatory injury molecules including TRAF6 and ROS in LPS-stimulated KCs. LPS stimulation induced LC3 and p62 mRNA and LC3 II and p62 protein expression in KCs. After urantide pretreatment, LC3 and p62 mRNA and LC3 II protein were downregulated, while p62 protein was upregulated in LPS-stimulated KCs. In addition, antiapoptotic protein Bcl-2 inhibition and proapoptotic protein cleaved caspase-3 increase were observed in LPS-stimulated KCs, and the effects were enhanced after urantide pretreatment in the study. We conclude that liver injury mediated by the UII/UT system is possibly associated with the activation of autophagy-related and apoptosis-resisted pathways of KCs in ALF.
The Impact of the COVID-19 Pandemic on Breast Reconstruction: A Canadian Perspective
Authors: Illmann Caroline F. , Doherty Christopher , Wheelock Margaret , Vorstenbosch Joshua , Lipa Joan E. , Zhong Toni , Isaac Kathryn V.
Published: July 2021

Background:

The COVID-19 pandemic has led to unprecedented challenges and restrictions in surgical access across Canada, including for breast reconstructive services which are an integral component of comprehensive breast cancer care. We sought to determine how breast reconstructive services are being restricted, and what strategies may be employed to optimize the provision of breast reconstruction through a pan-Canadian evaluation from the providers’ perspective.

Methods:

This was a cross-sectional survey of Canadian plastic and reconstructive surgeons who perform breast reconstruction. The 33-item web-based questionnaire was developed by a pan-Canadian working group of breast reconstruction experts and disseminated via email to members of the Canadian Society of Plastic Surgery. The questionnaire queried respondents on the impact of the COVID-19 pandemic and associated restrictions on surgeons’ breast reconstruction practice patterns and opinions on strategies for resource utilization.

Results:

Responses were received from 49 surgeons, who reported practicing in 8 of 10 Canadian provinces. Restrictions on the provision of breast reconstructive procedures were most limited during the First Wave of the COVID-19 pandemic, where all respondents reported at least some reduction in capacity and more than a quarter reporting complete cessation. Average reported reduction in capacity ranged from 31% to 78% across all 3 waves. Autologous, delayed, and prophylactic reconstructions were most commonly restricted.

Conclusion:

This study provides a pan-Canadian impact assessment on breast reconstructive services during the COVID-19 pandemic from the providers’ perspective. To uphold the standards of patient-centred care, a unified approach to strategically reorganize health care delivery now and in the future is needed.
Entrepreneurship and Innovation in the Bakery Industry: A Case Study of Ganesh Bakery
Authors: Mehdi Mokhalles M. , Rakshit Sandip , Sarma Tridib Ranjan , Joshi Mugdha , Nille Nikita
Published: July 2021

Shree Ganesh Bakery Nandani Private Limited was founded in Nandani city, Kolhapur, Maharastra (India) in 1991. The company was founded and spearheaded by Annasaheb Balasaheb Chakote and was in the business of manufacturing and retail of bakery food products. It was manufacturing 180 products majorly in the category of baked items, health-conscious food, sweet food, and namkeen (salted) food. It has a strong geographic presence across Maharashtra and other neighbouring Indian states, namely Goa, Karnataka and Andhra Pradesh through dealers and distributors. The company aimed to expand the business through regular development of new products, expansion of its distribution networks in the remaining areas of Maharashtra and its neighbouring states. However, it had difficulties in the supply of the new products to meet the consumer demand in targeted areas. In February 2017, Chakote aimed to devise a strategy to fulfil the planned expansion of the business.
Problems, complications, and reinterventions in 4893 onlay humeral lateralized reverse shoulder arthroplasties: a systematic review (part I—complications)
Authors: Ascione Francesco , Schiavone Panni Alfredo , Braile Adriano , Corona Katia , Toro Giuseppe , Capuano Nicola , Romano Alfonso M.
Published: July 2021

Background

Several modifications to the original Grammont reverse shoulder arthroplasty (RSA) design have been proposed to prevent distinctive issues, such as both glenoid and humeral lateralization. The aim of this systematic review was to determine rates of problems, complications, reoperations, and revisions after onlay lateralized humeral stem RSA, hypothesizing that these are design related.

Methods

This systematic review was performed in accordance with the PRISMA statement guidelines. A literature search was conducted (01.01.2000–14.04.2020) using PubMed, Cochrane Reviews, Scopus, and Google Scholar employing several combinations of keywords: “reverse shoulder arthroplasty,” “reverse shoulder prosthesis,” “inverse shoulder arthroplasty,” “inverse shoulder prosthesis,” “problems,” “complications,” “results,” “outcomes,” “reoperation,” “revision.”

Results

Thirty-one studies with 4893 RSA met inclusion criteria. The 892 postoperative problems and 296 postoperative complications represented overall problem and complication rates of 22.7% and 7.5%, respectively. Forty-one reoperations and 63 revisions resulted, with an overall reoperation rate of 1.7% and overall revision rate of 2.6%.

Conclusions

Problem, complication, and reintervention rates proved acceptable when implanting a high humeral lateralization stem in RSA. The most frequent problem was scapular notching (12.6%), and the most common postoperative complication was scapular stress fracture (1.8%). An overall humeral complication rate of 1.9% was identified, whereas short stems reported no humeral fractures or stem loosening. Infections (1.3%) proved to be the most common reason for component revision, and instability had a complication rate of 0.8%.

Level of evidence

Systematic review IV
Assessment of the sanitary quality of ready to eat sesame, a low moisture street food from Burkina Faso
Authors: Compaoré Muller K. A. , Bazie Bazoin Sylvain Raoul , Nikiema Marguerite E. M. , Dakené Virginie Marie , Dembélé René , Kpoda Dissinviel Stéphane , Kabré Elie , Barro Nicolas
Published: July 2021

Background

Microbial contamination of edible low moisture food poses a significant public health risk for human. In this study, the microbial quality of sweet dehulled sesame seed croquettes, salted dehulled sesame seed and the raw sesame seed, sold under ambient conditions were examined. The samples were collected in the cities of Burkina Faso. The first type is sweet dehulled sesame seed croquettes (n1 = 25); the second type is salted dehulled sesame seed (n2 = 25) and the third type is raw sesame seed (n3 = 25). Assessment of the microbial quality was based on the total aerobic mesophilic bacteria, the thermotolerant coliforms, the yeasts and moulds, the E. coli, and the Salmonella spp. using ISO methods.

Results

The results showed the presence of microorganisms varying from <1.0 to 1.72 × 105 CFU g− 1 for thermotolerant coliforms, from <1.0 to 6,12 × 106 CFU g− 1 for the total mesophilic aerobic flora and from <1.0 to 8.10 × 105 CFU g− 1 for yeasts and moulds. The higher contaminations rates were mostly observed in raw sesame seed samples. No E coli or Salmonella pathogens were detected. Based on international standards of dehydrated food, 50.67% of the ready to eat sesame are satisficing while 17.33% are acceptable and 32% are not satisficing.

Conclusion

Attention should be emphasized on the processing practices, especially in crowded places where RTE sesames seeds are mostly sold. The high numbers of all microbial groups in these sesame seed samples suggested that the production of RTE sesame seed should be improved by better hygiene. This study highlights also that RTE sesame seed might harbor a wide range of microorganisms when processes are weak of hygiene.
Translation, transcultural adaptation and validation to Brazilian Portuguese of tools for adverse drug reaction assessment in children
Authors: da Costa Lima Elisangela , de Barros Fernandes Thais , Freitas Adair , de Lima Sias Juliana Freire , Land Marcelo Gerardin Poirot , Aires Mariana Tschoepke , Bracken Louise , Peak Matthew
Published: July 2021

Background

Children are more vulnerable to adverse drug reactions (ADRs) due to complex changes in the body during the growth process and lack specific pharmacoepidemiologic studies. Causality and Avoidability assessment of ADRs are relevant to clinical guidelines development and pharmacovigilance. This study aimed to translate and transcultural adapt two new tools—Liverpool Causality Assessment Tool (LCAT) and the Liverpool Avoidability Assessment Tool (LAAT)—to Brazilian-Portuguese and evaluate the psychometric properties of these tools to analyse ADRs in Brazilian children.

Methods

The validation of the cross-cultural adaptation of tools was obtained by the functional (conceptual, semantic, operational, and measurement) equivalence between the original and translated versions of each instrument. The translated version of LCAT and LAAT was applied to assessing the twenty-six case reports of suspected adverse drug reactions in a Brazilian teaching paediatric hospital. The inter-rater reliability (a pharmacist and a physician) was evaluated using Cronbach’s alpha. The exact agreement percentages (%EA) and extreme disagreement (%ED) were computed. Overall Kappa index was calculated with a 95% confidence interval.

Results

There was a need to modify some terms translated into Portuguese for semantic and conceptual equivalence. The Cronbach’s alpha coefficient values obtained were 0.95 and 0.85, and the weighted Kappa (95% confidence interval) were 0.82 (0.67–0.97) and 0.68 (0.45–0.91) for LCAT and LAAT, respectively. The Brazilian-Portuguese versions of the LCAT and LAAT showed reliable and valid tools for the diagnosis and follow-up of ADRs in children.

Conclusion

The methodological approach allowed the translation, transcultural adaptation, and validation to Brazilian-Portuguese of two easy and quick to perform tools for causality and avoidability of ADRs in children by a multidisciplinary expert specialist committee, including the authors of original tools. We believe these versions may be applied by professionals (patient safety teams) and researchers in Brazil in groups or by a single reviewer.

Trial registration

This study was evaluated and approved by the Research Ethics Committee (Instituto de Pediatria e Puericultura Martagão Gesteira – Federal University of Rio de Janeiro – Number: 3.264.238.
Symptoms and signs of colorectal cancer, with differences between proximal and distal colon cancer: a prospective cohort study of diagnostic accuracy in primary care
Authors: Holtedahl Knut , Borgquist Lars , Donker Gé A. , Buntinx Frank , Weller David , Campbell Christine , Månsson Jörgen , Hammersley Victoria , Braaten Tonje , Parajuli Ranjan
Published: July 2021

Background

In an abdominal symptom study in primary care in six European countries, 511 cases of cancer were recorded prospectively among 61,802 patients 16 years and older in Norway, Denmark, Sweden, Netherlands, Belgium and Scotland. Colorectal cancer is one of the main types of cancer associated with abdominal symptoms; hence, an in-depth subgroup analysis of the 94 colorectal cancers was carried out in order to study variation in symptom presentation among cancers in different anatomical locations.

Method

Initial data capture was by completion of standardised forms containing closed questions about symptoms recorded during the consultation. Follow-up data were provided by the GP after diagnosis, based on medical record data made after the consultation. GPs also provided free text comments about the diagnostic procedure for individual patients. Fisher’s exact test was used to analyse differences between groups.

Results

Almost all symptoms recorded could indicate colorectal cancer. ‘Rectal bleeding’ had a specificity of 99.4% and a PPV of 4.0%. Faecal occult blood in stool (FOBT) or anaemia may indicate gastrointestinal bleeding: when these symptoms and signs were combined, sensitivity reached 57.5%, with 69.2% for cancer in the distal colon. For proximal colon cancers, none of 18 patients had ‘Rectal bleeding’ at the initial consultation, but three of the 18 did so at a later consultation. ‘Abdominal pain, lower part’, ‘Constipation’ and ‘Distended abdomen, bloating’ were less specific and also less sensitive than ‘Rectal bleeding’, and with PPV between 0.7% and 1.9%.

Conclusions

Apart from rectal bleeding, single symptoms did not reach the PPV 3% NICE threshold. However, supplementary information such as a positive FOBT or persistent symptoms may revise the PPV upwards. If a colorectal cancer is suspected by the GP despite few symptoms, the total clinical picture may still reach the NICE PPV threshold of 3% and justify a specific referral.
Daily, oral FMT for long-term maintenance therapy in ulcerative colitis: results of a single-center, prospective, randomized pilot study
Authors: Crothers Jessica W. , Chu Nathaniel D. , Nguyen Le Thanh Tu , Phillips Magen , Collins Cheryl , Fortner Karen , Del Rio-Guerra Roxana , Lavoie Brigitte , Callas Peter , Velez Mario , Cohn Aaron , Elliott Ryan J. , Wong Wing Fei , Vo Elaine , Wilcox Rebecca , Smith Mark , Kassam Zain , Budd Ralph , Alm Eric J. , Mawe Gary M. , Moses Peter L.
Published: July 2021

Background

Fecal microbiota transplantation (FMT) is a promising new strategy in the treatment of Inflammatory Bowel Disease, but long-term delivery systems are lacking. This randomized study was designed as a safety and feasibility study of long-term FMT in subjects with mild to moderate UC using frozen, encapsulated oral FMT (cFMT).

Methods

Subjects were randomized 1:1 to receive FMT induction by colonoscopy, followed by 12 weeks of daily oral administration of frozen encapsulated cFMT or sham therpay. Subjects were followed for 36 weeks and longitudenal clinical assessments included multiple subjective and objective markers of disease severity. Ribosomal 16S bacterial sequencing was used to assess donor-induced changes in the gut microbiota. Changes in T regulatory (Treg) and mucosal associated invariant T (MAIT) cell populations were evaluated by flow cytometry as an exploratory endpoint.

Results

Twelve subjects with active UC were randomized: 6 subjects completed the full 12-week course of FMT plus cFMT, and 6 subjects received sham treatment by colonic installation and longitudinal oral placebo capules. Chronic administration of cFMT was found to be safe and well-tolerated but home storage concerns exist. Protocol adherence was high, and none of the study subjects experienced FMT-associated treatment emergent adverse events. Two subjects that received cFMT achieved clinical remission versus none in the placebo group (95% CI = 0.38-infinity, p = 0.45). cFMT was associated with sustained donor-induced shifts in fecal microbial composition. Changes in MAIT cell cytokine production were observed in cFMT recipients and correlated with treatment response.

Conclusion

These pilot data suggest that daily encapsulated cFMT may extend the durability of index FMT-induced changes in gut bacterial community structure and that an association between MAIT cell cytokine production and clinical response to FMT may exist in UC populations. Oral frozen encapsulated cFMT is a promising FMT delivery system and may be preferred for longterm treatment strategies in UC and other chronic diseases but further evaluations will have to address home storage concerns. Larger trials should be done to explore the benefits of cFMT and to determine its long-term impacts on the colonic microbiome. Trial registration: ClinicalTrials.gov (NCT02390726). Registered 17 March 2015, https://clinicaltrials.gov/ct2/show/NCT02390726?term=NCT02390726&draw=2&rank=1.
Lung abscess secondary to lung cancer with a coinfection of Granulicatellaadiacens and other bacteria: a case report
Authors: Yang Shuo , Wu Liangliang , Xu Lili , Huang Xiang , Sun Xiaofeng , Yang Lan , Xu Ling
Published: July 2021

Background

Granulicatella adiacens is facultative anaerobic Gram-positive bacteria, which mainly involve bacterial endocarditis and bacteremia, but there are few reports of local suppurative infection. A case of lung abscess with a coinfection of Granulicatella adiacens and other bacteria in a lung cancer patient will be reported in this paper. To our knowledge, this is the first case report describing lung abscess due to G.adiacens.

Case presentation

A 52-year-old Chinese woman was admitted to the hospital, She complained of coughing and expectoration for 1 month, shortness of breath for half a month, and dyspnea for 1 day. After a series of examinations, she was diagnosed with lung abscess, pleural effusion, and bronchogenic carcinoma. Draining pus culture demonstrated Granulicatella adiacens. After more than 5 weeks of antibiotic therapies in total, she gradually recovered to fight against lung cancer.

Conclusion

This is the first reported lung abscess caused by G.adiacens. In immunosuppressed hosts, G.adiacens is a virulent pathogen associated with a spectrum of intrathoracic suppurative. Earlier diagnosis and proper drainage surgery with effective antibiotics treatment are very important, and antimicrobial treatment should be more than 5 weeks. When complex pulmonary infection interferes with the CT diagnosis, clinical suspicion of lung cancer should be increased if G.adiacens or Eikenella corrodens is detected from a pulmonary infection.
Predictors of mortality in patients with coronavirus disease 2019: a systematic review and meta-analysis
Authors: Shi Changcheng , Wang Limin , Ye Jian , Gu Zhichun , Wang Shuying , Xia Junbo , Xie Yaping , Li Qingyu , Xu Renjie , Lin Nengming
Published: July 2021

Background

Coronavirus disease 2019 (COVID-19) is associated with a high mortality rate, especially in patients with severe illness. We conducted a systematic review and meta-analysis to assess the potential predictors of mortality in patients with COVID-19.

Methods

PubMed, EMBASE, the Cochrane Library, and three electronic Chinese databases were searched from December 1, 2019 to April 29, 2020. Eligible studies reporting potential predictors of mortality in patients with COVID-19 were identified. Unadjusted prognostic effect estimates were pooled using the random-effects model if data from at least two studies were available. Adjusted prognostic effect estimates were presented by qualitative analysis.

Results

Thirty-six observational studies were identified, of which 27 were included in the meta-analysis. A total of 106 potential risk factors were tested, and the following important predictors were associated with mortality: advanced age, male sex, current smoking status, preexisting comorbidities (especially chronic kidney, respiratory, and cardio-cerebrovascular diseases), symptoms of dyspnea, complications during hospitalization, corticosteroid therapy and a severe condition. Additionally, a series of abnormal laboratory biomarkers of hematologic parameters, hepatorenal function, inflammation, coagulation, and cardiovascular injury were also associated with fatal outcome.

Conclusion

We identified predictors of mortality in patients with COVID-19. These findings could help healthcare providers take appropriate measures and improve clinical outcomes in such patients.
Community based screening for sickle haemoglobin among pregnant women in Benue State, Nigeria: I-Care-to-Know, a Healthy Beginning Initiative
Authors: Ezenwosu Osita U. , Itanyi Ijeoma U. , Nnodu Obiageli E. , Ogidi Amaka G. , Mgbeahurike Fabian , Ezeanolue Echezona E.
Published: July 2021

Background

Haemoglobin genotype screening at prenatal care offers women an opportunity to be aware of their genotype, receive education on sickle cell disease (SCD) and may increase maternal demand for SCD newborn screening. In developed countries, most pregnant women who access prenatal care and deliver at the hospital receive haemoglobin genotype screening. In settings with low prenatal care attendance and low hospital deliveries, community-based screening may provide similar opportunity for pregnant women. We assessed the feasibility and acceptability of integrating haemoglobin genotype screening into an existing community-based HIV program.

Methods

Onsite community-based integrated testing for HIV, hepatitis B virus and haemoglobin electrophoresis, were conducted for pregnant women and their male partners. Community Health Advisors implementing the NIH and PEPFAR-supported Healthy Beginning Initiative (HBI) program provided education on SCD, collected blood sample for haemoglobin electrophoresis and provided test results to participants enrolled into the HBI program. We concurrently conducted a cross-sectional study using a pretested, semi-structured, interviewer administered questionnaire to collect demographic data and assess awareness of individual haemoglobin “genotype” among HBI pregnant women participants.

Results

In this study, 99.9% (10,167/10,168) of pregnant women who received education on SCD accepted and completed the survey, had blood drawn for haemoglobin electrophoresis and received their results. A majority of participating pregnant women (97.0%) were not aware of their haemoglobin “genotype”. Among the participants who were incorrect about their haemoglobin “genotype”, 41.1% (23/56) of women who reported their haemoglobin “genotype” as AA were actually AS. The odds of haemoglobin “genotype” awareness was higher among participants who were in younger age group, completed tertiary education, had less number of pregnancies, and attended antenatal care. Overall prevalence of sickle cell trait (AS) was 18.7%.

Conclusions

It is feasible to integrate haemoglobin “genotype” testing into an existing community-based maternal-child program. Most pregnant women who were unaware of their haemoglobin “genotype” accepted and had haemoglobin genotype testing, and received their test results. Increasing parental awareness of their own haemoglobin “genotype” could increase their likelihood of accepting newborn screening for SCD.
Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients
Authors: Gao Xingjie , Zhao Chunyan , Zhang Nan , Cui Xiaoteng , Ren Yuanyuan , Su Chao , Wu Shaoyuan , Yao Zhi , Yang Jie
Published: July 2021

Background

The clinical pathologic stages (stage I, II, III-IV) of hepatocellular carcinoma (HCC) are closely linked to the clinical prognosis of patients. This study aims at investigating the gene expression and mutational profile in different clinical pathologic stages of HCC.

Methods

Based on the TCGA-LIHC cohort, we utilized a series of analytical approaches, such as statistical analysis, random forest, decision tree, principal component analysis (PCA), to identify the differential gene expression and mutational profiles. The expression patterns of several targeting genes were also verified by analyzing the Chinese HLivH060PG02 HCC cohort, several GEO datasets, HPA database, and diethylnitrosamine-induced HCC mouse model.

Results

We identified a series of targeting genes with copy number variation, which is statistically associated with gene expression. Non-synonymous mutations mainly existed in some genes (e.g.,TTN, TP53, CTNNB1). Nevertheless, no association between gene mutation frequency and pathologic stage distribution was detected. The random forest and decision tree modeling analysis data showed a group of genes related to different HCC pathologic stages, including GAS2L3 and SEMA3F. Additionally, our PCA data indicated several genes associated with different pathologic stages, including SNRPA and SNRPD2. Compared with adjacent normal tissues, we observed a highly expressed level of GAS2L3, SNRPA, and SNRPD2 (P = 0.002) genes in HCC tissues of our HLivH060PG02 cohort. We also detected the high expression pattern of GAS2L3, SEMA3F, SNRPA, and SNRPD2 in the datasets of GSE102079, GSE76427, GSE64041, GSE121248, GSE84005, and the qPCR assay using diethylnitrosamine-induced HCC mouse model. Moreover, SEMA3F and SNRPD2 protein were highly stained in the HCC tissues of the HPA database. The high expression level of these four genes was associated with the poor survival prognosis of HCC cases.

Conclusions

Our study provides evidence regarding the gene expression and mutational profile in different clinical pathologic stages of TCGA HCC cases. Identifying four targeting genes, including GAS2L3, SNRPA, SNRPD2, and SEMA3F, offers insight into the molecular mechanisms associated with different prognoses of HCC.
The correlation of next-generation sequencing-based genotypic profiles with clinicopathologic characteristics in NPM1-mutated acute myeloid leukemia
Authors: Wang Biao , Yang Bin , Wu Wei , Liu Xuan , Li Haiqian
Published: July 2021

The purpose of this study was to analyze the association between next-generation sequencing (NGS) genotypic profiles and conventional clinicopathologic characteristics in patients with acute myeloid leukemia (AML) with NPM1 mutation (NPM1mut). We selected 238 NPM1mut patients with available NGS information on 112 genes related to blood diseases using the χ2 and Mann-Whitney U tests and a multivariable logistic model to analyze the correlation between genomic alterations and clinicopathologic parameters. Compared with the NPM1mut/FLT3-ITD(−) group, the NPM1mut/FLT3-ITD(+) group presented borderline frequent M5 morphology [78/143 (54.5%) vs. 64/95 (67.4%); P = 0.048], higher CD34- and CD7-positive rates (CD34: 20.6% vs. 47.9%, P < 0.001; CD7: 29.9% vs. 61.5%, P < 0.001) and a lack of favorable−/adverse-risk karyotypes (6.4% vs. 0%; P = 0.031). In the entire NPM1mut cohort, 240 NPM1 mutants were identified, of which 10 (10/240, 4.2%) were missense types. When confining the analysis to the 205 cases with NPM1mut insertions/deletions-type and normal karyotype, multivariable logistic analysis showed that FLT3-ITD was positively correlated with CD34 and CD7 expressions (OR = 5.29 [95% CI 2.64–10.60], P < 0.001; OR = 3.47 [95% CI 1.79–6.73], P < 0.001, respectively). Ras-pathway mutations were positively correlated with HLA-DR expression (OR = 4.05 [95% CI 1.70–9.63], P = 0.002), and KRAS mutations were negatively correlated with MPO expression (OR = 0.18 [95% CI 0.05–0.62], P = 0.007). DNMT3A-R882 was positively correlated with CD7 and HLA-DR expressions (OR = 3.59 [95% CI 1.80–7.16], P < 0.001; OR = 13.41 [95% CI 4.56–39.45], P < 0.001, respectively). DNMT3A mutation was negatively correlated with MPO expression (OR = 0.35 [95% CI 1.48–8.38], P = 0.004). TET2/IDH1 mutations were negatively correlated with CD34 and CD7 expressions (OR = 0.26 [95% CI 0.11–0.62], P = 0.002; OR = 0.30 [95% CI 0.14–0.62], P = 0.001, respectively) and positively correlated with MPO expression (OR = 3.52 [95% CI 1.48–8.38], P = 0.004). In conclusion, NPM1mut coexisting mutations in signaling pathways (FLT3-ITD and Ras-signaling pathways) and methylation modifiers (DNMT3A and TET2/IDH1) are linked with the expressions of CD34, CD7, HLA-DR and MPO, thereby providing a mechanistic explanation for the immunophenotypic heterogeneity of this AML entity.
Computational analysis for identification of early diagnostic biomarkers and prognostic biomarkers of liver cancer based on GEO and TCGA databases and studies on pathways and biological functions affecting the survival time of liver cancer
Authors: Gao Shiyong , Gang Jian , Yu Miao , Xin Guosong , Tan Huixin
Published: July 2021

Background

Liver cancer is the sixth most commonly diagnosed cancer and the fourth most common cause of cancer death. The purpose of this work is to find new diagnostic biomarkers or prognostic biomarkers and explore the biological functions related to the prognosis of liver cancer.

Methods

GSE25097 datasets were firstly obtained and compared with TCGA LICA datasets and an analysis of the overlapping differentially expressed genes (DEGs) was conducted. Cytoscape was used to screen out the Hub Genes among the DEGs. ROC curve analysis was used to screen the Hub Genes to determine the genes that could be used as diagnostic biomarkers. Kaplan-Meier analysis and Cox proportional hazards model screened genes associated with prognosis biomarkers, and further Gene Set Enrichment Analysis was performed on the prognosis genes to explore the mechanism affecting the survival and prognosis of liver cancer patients.

Results

790 DEGs and 2162 DEGs were obtained respectively from the GSE25097 and TCGA LIHC data sets, and 102 Common DEGs were identified by overlapping the two DEGs. Further screening identified 22 Hub Genes from 102 Common DEGs. ROC and survival curves were used to analyze these 22 Hub Genes and it was found that there were 16 genes with a value of AUC > 90%. Among these, the expression levels of ESR1,SPP1 and FOSB genes were closely related to the survival time of liver cancer patients. Three common pathways of ESR1, FOBS and SPP1 genes were identified along with seven common pathways of ESR1 and SPP1 genes and four common pathways of ESR1 and FOSB genes.

Conclusions

SPP1, AURKA, NUSAP1, TOP2A, UBE2C, AFP, GMNN, PTTG1, RRM2, SPARCL1, CXCL12, FOS, DCN, SOCS3, FOSB and PCK1 can be used as diagnostic biomarkers for liver cancer, among which FOBS and SPP1 genes can also be used as prognostic biomarkers. Activation of the cell cycle-related pathway, pancreas beta cells pathway, and the estrogen signaling pathway, while on the other hand inhibition of the hallmark heme metabolism pathway, hallmark coagulation pathway, and the fat metabolism pathway may promote prognosis in liver cancer patients.
Towards comprehensive mental health care: experiences and challenges of psychosocial care in Brazil
Authors: Sampaio Mariá Lanzotti , Bispo Júnior José Patrício
Published: July 2021

Background

Recommendations are in place for mental health (MH) care to be developed into a comprehensive, people-centred perspective and organised primarily through community services. In recent decades, Brazil has promoted psychiatric reform aimed at transforming the hospital-centred model into a psychosocial model of MH. However, current political and economic changes threaten this reform. This article analyses the comprehensive MH care offered by a Psychosocial Care Network (Rede de Atenção Psicossocial – RAPS) in Brazil.

Methods

The study involved semi-structured in-depth interviews with 33 stakeholders (policymakers, health professionals, and MH service users) and direct observation of MH services members of the RAPS. Data were analysed using framework analysis with the following dimensions: mental health services access, long-term mental health care, comprehensive mental health care, and crisis patient care.

Results

Results indicated progression towards comprehensive MH care provision. We identified MH care provided primarily by community services, featuring an ‘open door’ policy, development of localised actions and a search for autonomy. Deinstitutionalisation principles and the psychosocial model support a comprehensive view of MH by policy makers, MH professionals, and users. However, difficulties in providing comprehensive care remain, with the main challenges being insufficient services offered and difficulties in user access at all levels of care, fragile integration between services, lack of clear definitions of the responsibilities of each service, discontinuity of care, limitations in family support, and fragility in crisis patient care.

Conclusion

We highlight the need to increase funding and services of RAPS, qualification of staff professional, family support, and development of strategies for integrating services. Support and expansion of MH care depend on strengthening the Brazilian health system, which is in danger of being dismantled.