bluuebunny/crossref_metadata_2025 huggingface dataset:
Perioperative consultative hematology: can you clear my patient for a procedure?
Authors: Burnett Allison Elaine , Ragheb Bishoy , Kaatz Scott
Published: December 2021

Periprocedural management of antithrombotics is a common but challenging clinical scenario that renders patients vulnerable to potential adverse events such as bleeding and thrombosis. Over the past decade, periprocedural antithrombotic approaches have changed considerably with the advent of direct oral anticoagulants (DOACs), as well as a paradigm shift away from bridging in many warfarin patients. Successfully navigating this high-risk period relies on a number of individualized patient assessments conducted within a framework of standardized, systematic approaches. It also requires a thorough understanding of antithrombotic pharmacokinetics, multidisciplinary coordination of care, and comprehensive patient education and empowerment. In this article, we provide clinicians with a practical, stepwise approach to periprocedural management of antithrombotic agents through case-based examples of relevant clinical scenarios.
Heparin-induced thrombocytopenia and cardiovascular surgery
Authors: Pishko Allyson M. , Cuker Adam
Published: December 2021

Clinicians generally counsel patients with a history of heparin-induced thrombocytopenia (HIT) to avoid heparin products lifelong. Although there are now many alternative (nonheparin) anticoagulants available, heparin avoidance remains challenging for cardiac surgery. Heparin is often preferred in the cardiac surgery setting based on the vast experience with the agent, ease of monitoring, and reversibility. To “clear” a patient with a history of HIT for cardiac surgery, hematologists must first confirm the diagnosis of HIT, which can be challenging due to the ubiquity of heparin exposure and frequency of thrombocytopenia in patients in the cardiac intensive care unit. Next, the “phase of HIT” (acute HIT, subacute HIT A/B, or remote HIT) should be established based on platelet count, immunoassay for antibodies to platelet factor 4/heparin complexes, and a functional assay (eg, serotonin release assay). As long as the HIT functional assay remains positive (acute HIT or subacute HIT A), cardiac surgery should be delayed if possible. If surgery cannot be delayed, an alternative anticoagulant (preferably bivalirudin) may be used. Alternatively, heparin may be used with either preoperative/intraoperative plasma exchange or together with a potent antiplatelet agent. The optimal strategy among these options is not known, and the choice depends on institutional experience and availability of alternative anticoagulants. In the later phases of HIT (subacute HIT B or remote HIT), brief intraoperative exposure to heparin followed by an alternative anticoagulant as needed in the postoperative setting is recommended.
Optimal strategies for carrier screening and prenatal diagnosis of α- and β-thalassemia
Authors: Mensah Cheryl , Sheth Sujit
Published: December 2021

The thalassemias are inherited quantitative disorders of hemoglobin synthesis with a significant worldwide burden, which result in a wide spectrum of disease from the most severe transfusion-dependent form to the mildest asymptomatic carrier state. In this article, we discuss the importance of carrier, prenatal, and newborn screening for thalassemia. We examine the rationale for who should be screened and when, as well as the current methodology for screening. Deficiencies in the newborn screening program are highlighted as well. With the advent of inexpensive and rapid genetic testing, this may be the most practical method of screening in the future, and we review the implications of population-based implementation of this strategy. Finally, a case-based overview of the approach for individuals with the trait as well as prospective parents who have a potential fetal risk of the disease is outlined.
How to choose first salvage therapy in Hodgkin lymphoma: traditional chemotherapy vs novel agents
Authors: Driessen Julia , Tonino Sanne H. , Moskowitz Alison J. , Kersten Marie José
Published: December 2021

Approximately 10% to 30% of patients with classical Hodgkin lymphoma (cHL) develop relapsed or refractory (R/R) disease. Of those patients, 50% to 60% show long-term progression-free survival after standard salvage chemotherapy followed by high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT). In the past decade, novel therapies have been developed, such as the CD30-directed antibody–drug conjugate brentuximab vedotin and immune checkpoint inhibitors, which have greatly extended the treatment possibilities for patients with R/R cHL. Several phase 1/2 clinical trials have shown promising results of these new drugs as monotherapy or in combination with chemotherapy, but unfortunately, very few randomized phase 3 trials have been performed in this setting, making it difficult to give evidence-based recommendations for optimal treatment sequencing. Two important goals for the improvement in the treatment of R/R cHL can be identified: (1) increasing long-term progression-free and overall survival by optimizing risk-adapted treatment and (2) decreasing toxicity in patients with a low risk of relapse of disease by evaluating the need for HDCT/ASCT in these patients. In this review, we discuss treatment options for patients with R/R cHL in different settings: patients with a first relapse, primary refractory disease, and in patients who are ineligible or unfit for ASCT. Results of clinical trials investigating novel therapies or strategies published over the past 5 years are summarized.
Pregnancy in special populations: challenges and solutions practical aspects of managing von Willebrand disease in pregnancy
Authors: Turan Ozlem , Kadir Rezan Abdul
Published: December 2021

Pregnancy and childbirth pose an important hemostatic challenge for women with von Willebrand disease (VWD) and can be associated with an increased risk of maternal and neonatal bleeding complications. VWD is a genetically and clinically heterogeneous bleeding disorder caused by a deficiency or an abnormality in the function of von Willebrand factor. Understanding inheritance pattern, hemostatic response to pregnancy, and response to treatment is essential for provision of individualized obstetric care and optimal outcome. A multidisciplinary approach to management with a close liaison between the obstetric team and the hemophilia treatment center is required for continuity of care from preconception counseling through to antenatal, peripartum, and postpartum care. Delivery plan must be coordinated by the multidisciplinary team and include decisions on place and mode of delivery, implementation of safe analgesia/anesthesia, and peripartum hemostasis. In this clinical case-based review, we aim to deliver evidence-based practical guidance for challenges encountered during pregnancy and management of childbirth and puerperium.
Evidence-Based Minireview: In young children with severe sickle cell disease, do the benefits of HLA-identical sibling donor HCT outweigh the risks?
Authors: Shah Niketa , Krishnamurti Lakshmanan
Published: December 2021

In case 1, a 14-month-old male child with sickle cell disease (SCD) was referred for evaluation for an allogeneic hematopoietic stem cell transplant (HCT). The patient had a history of dactylitis 3 times in his first year of life and febrile episodes twice at the consult. His 4-year-old sister was found to be human leukocyte antigen (HLA) identical. The patient was started on hydroxyurea (HU) at 2.5 years of age. His parents again sought consultation when he was 5 years old because of concerns about his medical condition. At the time, the patient had experienced 2 vaso-occlusive pain episodes (VOEs) requiring hospitalization during the previous 2 years. He had also experienced intermittent pain crises requiring rest at home for 2 to 3 days. The child has not attended school in person due to the COVID-19 pandemic. The family is considering HCT but is ambivalent about it because of potential toxicity. In case 2, an 8-year-old female child is 3 years out from HCT for SCD from her HLA-identical sibling. Before HCT, despite receiving HU, she had experienced >5 VOEs requiring hospitalization and 2 episodes of acute chest syndromes in the previous 3 years. She had also been missing almost 50 days of school days each year. After HCT, she is now attending school regularly and participating in all normal age-appropriate activities. The parents believe that HCT has been transformative in their child's life.
Clinical characteristics, risk factors and outcomes in patients with severe COVID-19 registered in the International Severe Acute Respiratory and Emerging Infection Consortium WHO clinical characterisation protocol: a prospective, multinational, multicentre, observational study
Authors: Reyes Luis Felipe , Murthy Srinivas , Garcia-Gallo Esteban , Irvine Mike , Merson Laura , Martin-Loeches Ignacio , Rello Jordi , Taccone Fabio S. , Fowler Robert A. , Docherty Annemarie B. , Kartsonaki Christiana , Aragao Irene , Barrett Peter W. , Beane Abigail , Burrell Aidan , Cheng Matthew Pellan , Christian Michael D. , Cidade Jose Pedro , Citarella Barbara Wanjiru , Donnelly Christl A. , Fernandes Susana M. , French Craig , Haniffa Rashan , Harrison Ewen M. , Ho Antonia Ying Wai , Joseph Mark , Khan Irfan , Kho Michelle E. , Kildal Anders Benjamin , Kutsogiannis Demetrios , Lamontagne François , Lee Todd C. , Bassi Gianluigi Li , Lopez Revilla Jose Wagner , Marquis Catherine , Millar Jonathan , Neto Raul , Nichol Alistair , Parke Rachael , Pereira Rui , Poli Sergio , Povoa Pedro , Ramanathan Kollengode , Rewa Oleksa , Riera Jordi , Shrapnel Sally , Silva Maria Joao , Udy Andrew , Uyeki Timothy , Webb Steve A. , Wils Evert-Jan , Rojek Amanda , Olliaro Piero L. ,   ISARIC Clinical Characterisation Group
Published: December 2021

Due to the large number of patients with severe coronavirus disease 2019 (COVID-19), many were treated outside the traditional walls of the intensive care unit (ICU), and in many cases, by personnel who were not trained in critical care. The clinical characteristics and the relative impact of caring for severe COVID-19 patients outside the ICU is unknown. This was a multinational, multicentre, prospective cohort study embedded in the International Severe Acute Respiratory and Emerging Infection Consortium World Health Organization COVID-19 platform. Severe COVID-19 patients were identified as those admitted to an ICU and/or those treated with one of the following treatments: invasive or noninvasive mechanical ventilation, high-flow nasal cannula, inotropes or vasopressors. A logistic generalised additive model was used to compare clinical outcomes among patients admitted or not to the ICU. A total of 40 440 patients from 43 countries and six continents were included in this analysis. Severe COVID-19 patients were frequently male (62.9%), older adults (median (interquartile range (IQR), 67 (55–78) years), and with at least one comorbidity (63.2%). The overall median (IQR) length of hospital stay was 10 (5–19) days and was longer in patients admitted to an ICU than in those who were cared for outside the ICU (12 (6–23) daysversus8 (4–15) days, p<0.0001). The 28-day fatality ratio was lower in ICU-admitted patients (30.7% (5797 out of 18 831)versus39.0% (7532 out of 19 295), p<0.0001). Patients admitted to an ICU had a significantly lower probability of death than those who were not (adjusted OR 0.70, 95% CI 0.65–0.75; p<0.0001). Patients with severe COVID-19 admitted to an ICU had significantly lower 28-day fatality ratio than those cared for outside an ICU.
Investigating age and regional effects on the relation between the incidence of heat-related ambulance transport and daily maximum temperature or WBGT
Authors: Ueno Satoru , Hayano Daisuke , Noguchi Eiichi , Aruga Tohru
Published: December 2021

Background

Although age and regional climate are considered to have effects on the incidence ratio of heat-related illness, quantitative estimation of age or region on the effect of occurring temperature for heat stroke is limited.

Methods

By utilizing data on the number of daily heat-related ambulance transport (HAT) in each of three age groups (7–17, 18–64, 65 years old, or older) and 47 prefectures in Japan, and daily maximum temperature (DMT) or Wet Bulb Globe Temperature (DMW) of each prefecture for the summer season, the effects of age and region on heat-related illness were studied. Two-way ANOVA was used to analyze the significance of the effect of age and 10 regions in Japan on HAT. The population-weighted average of DMT or DMW measured at weather stations in each prefecture was used as DMT or DMW for each prefecture. DMT or DMW when HAT is one in 100,000 people (T1 and W1, respectively) was calculated for each age category and prefecture as an indicator of heat acclimatization. The relation between T1 or W1 and average DMT or DMW of each age category and prefecture were also analyzed.

Results

HAT of each age category and prefecture was plotted nearly on the exponential function of corresponding DMT or DMW. Average R2 of the regression function in 47 prefectures in terms of DMW was 0.86, 0.93, and 0.94 for juveniles, adults, and elderly, respectively. The largest regional difference of W1 in 47 prefectures was 4.5 and 4.8 °C for juveniles and adults, respectively between Hokkaido and Tokyo, 3.9 °C for elderly between Hokkaido and Okinawa. Estimated W1 and average DMT or DMW during the summer season for 47 prefectures was linearly related. Regarding age difference, the regression line showed that W1 of the prefecture for DMW at 30 °C of WBGT was 31.1 °C, 32.4 °C, and 29.8 °C for juveniles, adults, and elderly, respectively.

Conclusions

Age and regional differences affected the incidence of HAT. Thus, it is recommended that public prevention measures for heat-related disorders take into consideration age and regional variability.
Network-based cancer genomic data integration for pattern discovery
Authors: Zhu Fangfang , Li Jiang , Liu Juan , Min Wenwen
Published: December 2021

Background

Since genes involved in the same biological modules usually present correlated expression profiles, lots of computational methods have been proposed to identify gene functional modules based on the expression profiles data. Recently, Sparse Singular Value Decomposition (SSVD) method has been proposed to bicluster gene expression data to identify gene modules. However, this model can only handle the gene expression data where no gene interaction information is integrated. Ignoring the prior gene interaction information may produce the identified gene modules hard to be biologically interpreted.

Results

In this paper, we develop a Sparse Network-regularized SVD (SNSVD) method that integrates a prior gene interaction network from a protein protein interaction network and gene expression data to identify underlying gene functional modules. The results on a set of simulated data show that SNSVD is more effective than the traditional SVD-based methods. The further experiment results on real cancer genomic data show that most co-expressed modules are not only significantly enriched on GO/KEGG pathways, but also correspond to dense sub-networks in the prior gene interaction network. Besides, we also use our method to identify ten differentially co-expressed miRNA-gene modules by integrating matched miRNA and mRNA expression data of breast cancer from The Cancer Genome Atlas (TCGA). Several important breast cancer related miRNA-gene modules are discovered.

Conclusions

All the results demonstrate that SNSVD can overcome the drawbacks of SSVD and capture more biologically relevant functional modules by incorporating a prior gene interaction network. These identified functional modules may provide a new perspective to understand the diagnostics, occurrence and progression of cancer.
Postpartum contraceptive practices among urban and peri-urban women in North India: a mixed-methods cohort study protocol
Authors: Roy Nivedita , Adhikary Priyanka , Kabra Rita , Kiarie James , Mburu Gitau , Dhabhai Neeta , Chowdhury Ranadip , Mazumder Sarmila
Published: December 2021

Background

Postpartum family planning (PPFP) helps women space childbirths, increase exclusive breastfeeding and prevent unintended pregnancies, leading to reduction in maternal, infant and child morbidities and mortality. Unmet need of family planning is highest among women in the postpartum period due to lack of knowledge, cultural and religious barriers, access barriers and low antenatal care service utilization. However, in spite of low prevalence of postpartum family planning practices, birth-to-birth interval is reportedly high in Delhi, India. This study explores the postpartum contraception practices and the relationship between use of postpartum contraception and subsequent child linear growth.

Methods

This is a mixed method cohort study on PPFP and is nested within an ongoing “Women and Infants Integrated Interventions for Growth Study” (WINGS). Married women aged 18–30 years who have delivered a live baby are recruited for quantitative interviews at 6 weeks, 6, 12, and 24 months postpartum. In-depth interviews are conducted with a randomly selected sub-sample of women at each of the four time points, 35 husbands and 20 local service providers to understand their perspectives on PPFP practices.

Discussion

The findings from the study will provide useful insights into couples’ contraception preferences and choice of contraception, modern and traditional, initiation time and the effect of birth spacing and contraception use on subsequent linear growth of the child. This knowledge will be of significant public health relevance and will help in designing appropriate interventions for appropriate postpartum contraception use and delivery strategies. The study aims to work address the Sexual and Reproductive Health and Rights goal of promoting reproductive health, voluntary and safe sexual and reproductive choices for women.

Trial registration

Trial registration number: CTRI/2020/03/023954.
New Zealand women’s experiences of managing gestational diabetes through diet: a qualitative study
Authors: Lawrence R. L. , Ward K. , Wall C. R. , Bloomfield F. H.
Published: December 2021

Background

For women with gestational diabetes mellitus (GDM) poor dietary choices can have deleterious consequences for both themselves and their baby. Diet is a well-recognised primary strategy for the management of GDM. Women who develop GDM may receive dietary recommendations from a range of sources that may be inconsistent and are often faced with needing to make several dietary adaptations in a short period of time to achieve glycaemic control. The aim of this study was to explore how women diagnosed with GDM perceive dietary recommendations and how this information influences their dietary decisions during pregnancy and beyond.

Methods

Women diagnosed with GDM before 30 weeks’ gestation were purposively recruited from two GDM clinics in Auckland, New Zealand. Data were generated using semi-structured interviews and thematic analysed to identify themes describing women’s perceptions and experiences of dietary recommendations for the management of GDM.

Results

Eighteen women from a diverse range of sociodemographic backgrounds participated in the study. Three interconnected themes described women’s perceptions of dietary recommendations and experiences in managing their GDM through diet: managing GDM is a balancing act; using the numbers as evidence, and the GDM timeframe. The primary objective of dietary advice was perceived to be to control blood glucose levels and this was central to each theme. Women faced a number of challenges in adhering to dietary recommendations. Their relationships with healthcare professionals played a significant role in their perception of advice and motivation to adhere to recommendations. Many women perceived the need to follow dietary recommendations to be temporary, with few planning to continue dietary adaptations long-term.

Conclusions

The value of empathetic, individually tailored advice was highlighted in this study. A greater emphasis on establishing healthy dietary habits not just during pregnancy but for the long-term health of both mother and baby is needed.
Predictors of wealth-related inequality in institutional delivery: a decomposition analysis using Nepal multiple Indicator cluster survey (MICS) 2019
Authors: Bhusal Umesh Prasad
Published: December 2021

Background

Inequality in maternal healthcare use is a major concern for low-and middle-income countries (LMICs). Maternal health indicators at the national level have markedly improved in the last couple of decades in Nepal. However, the progress is not uniform across different population sub-groups. This study aims to identify the determinants of institutional delivery, measure wealth-related inequality, and examine the key components that explain the inequality.

Methods

Most recent nationally representative Multiple Indicator Cluster Survey (MICS) 2019 was used to extract data about married women (15-49 years) with a live birth within two years preceding the survey. Logistic regression models were employed to assess the association of independent variables with the institutional delivery. The concentration curve (CC) and concentration index (CIX) were used to analyze the inequality in institutional delivery. Wealth index scores were used as a socio-economic variable to rank households. Decomposition was performed to identify the determinants that explain socio-economic inequality.

Results

The socio-economic status of households to which women belong was a significant predictor of institutional delivery, along with age, parity, four or more ANC visits, education status of women, area of residence, sex of household head, religious belief, and province. The concentration curve was below the line of equality and the relative concentration index (CIX) was 0.097 (p < 0.001), meaning the institutional delivery was disproportionately higher among women from wealthy groups. The decomposition analysis showed the following variables as the most significant contributor to the inequality: wealth status of women (53.20%), education of women (17.02%), residence (8.64%) and ANC visit (6.84%).

Conclusions

To reduce the existing socio-economic inequality in institutional delivery, health policies and strategies should focus more on poorest and poor quintiles of the population. The strategies should also focus on raising the education level of women especially from the rural and relatively backward province (Province 2). Increasing antenatal care (ANC) coverage through outreach campaigns is likely to increase facility-based delivery and decrease inequality. Monitoring of healthcare indicators at different sub-population levels (for example wealth, residence, province) is key to ensure equitable improvement in health status and achieve universal health coverage (UHC).
Association of chronic diseases and lifestyle factors with suicidal ideation among adults aged 18–69 years in Eswatini: evidence from a population-based survey
Authors: Motsa Mfundi President Sebenele , Chiou Hung-Yi , Chen Yi-Hua
Published: December 2021

Background

How chronic diseases and lifestyle affect suicidal ideation in the sub-Saharan region remains unclear. We investigated the association of chronic diseases and lifestyle with suicidal ideation in the past year and the potential modifying role of sociodemographic status on this association. The findings can guide suicide prevention interventions.

Methods

We analyzed 3026 respondents from the World Health Organization STEPwise approach to noncommunicable disease risk factor surveillance conducted in Eswatini in 2014. The outcome was past-year suicidal ideation, and the main predictors were chronic diseases and lifestyle. Multiple logistic regression was used to estimate predictors, and subgroup analysis was performed to assess effect modification.

Results

The prevalence of past-year suicidal ideation was 9.9%. After adjustment for covariates, including sex, marital status, employment status, and education level, individuals aged 18–30 years (adjusted odds ratio [aOR]: 2.27, 95% confidence interval [CI]: 1.22–4.22) were more likely to have had past-year suicidal ideation than those aged 45–69 years. After adjustment for covariates among employed individuals, having high blood pressure (aOR: 3.38, 95% CI: 1.54–7.40), not exercising (aOR: 2.65, 95% CI: 1.09–6.39), drinking alcohol (aOR: 2.40, 95% CI: 1.14–5.05), being aged 18–30 years (aOR: 3.50, 95% CI: 1.01–12.1), and being exposed to threats (aOR: 2.37, 95% CI: 1.01–5.53) were significantly associated with past-year suicidal ideation.

Conclusions

Among currently employed individuals, having high blood pressure, not exercising, and drinking alcohol were associated with past-year suicidal ideation. The findings highlight the importance of developing and strengthening systems for early identification of suicidal ideation risk.
Identification of prognostic and therapeutic value of CC chemokines in Urothelial bladder cancer: evidence from comprehensive bioinformatic analysis
Authors: Li Yuxin , Chen Xiong , Li Dongjie , Yang Zhiming , Bai Yao , Hu Sheng , Liu Zhenyu , Gu Jie , Zhang XiaoBo
Published: December 2021

Background

Urothelial bladder cancer (BC) is one of the most prevalent malignancies with high mortality and high recurrence rate. Angiogenesis, tumor growth and metastasis of multiple cancers are partly modulated by CC chemokines. However, we know little about the function of distinct CC chemokines in BC.

Methods

ONCOMINE, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan–Meier plotter, cBioPortal, GeneMANIA, and TIMER were used for analyzing differential expression, prognostic value, protein–protein interaction, genetic alteration and immune cell infiltration of CC chemokines in BC patients based on bioinformatics.

Results

The results showed that transcriptional levels of CCL2/3/4/5/14/19/21/23 in BC patients were significantly reduced. A significant relation was observed between the expression of CCL2/11/14/18/19/21/23/24/26 and the pathological stage of BC patients. BC patients with high expression levels of CCL1, CCL2, CCL3, CCL4, CCL5, CCL8, CCL13, CCL15, CCL17, CCL18, CCL19, CCL22, CCL25, CCL27 were associated with a significantly better prognosis. Moreover, we found that differentially expressed CC chemokines are primarily correlated with cytokine activity, chemokines receptor binding, chemotaxis, immune cell migration. Further, there were significant correlations among the expression of CC chemokines and the infiltration of several types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells).

Conclusions

This study is an analysis to the potential role of CC chemokines in the therapeutic targets and prognostic biomarkers of BC, which gives a novel insight into the relationship between CC chemokines and BC.
Accuracy of photogrammetry, intraoral scanning, and conventional impression techniques for complete-arch implant rehabilitation: an in vitro comparative study
Authors: Ma Bowen , Yue Xinxin , Sun Yujie , Peng Lingyan , Geng Wei
Published: December 2021

Background

To compare the accuracy of photogrammetry, intraoral scanning and conventional impression techniques for complete-arch implant rehabilitation.

Methods

A master cast containing 6 implant abutment replicas was fabricated. Group PG: digital impressions were taken 10 times using a photogrammetry system; Group IOS: intraoral scanning was performed to fabricate 10 digital impressions; Group CNV: splinted open-tray impression technique was used to fabricate 10 definitive casts. The master cast and conventional definitive casts were digitized with a laboratory reference scanner. For all STL files obtained, scan bodies were converted to implant abutment replicas using a digital library. The accuracy of a digitizer was defined by 2 main parameters, trueness and precision. "Trueness" was used to describe the deviation between test files and reference file, and "precision" was used to describe the closeness between test files. Then, the trueness and precision of three impression techniques were evaluated and statistically compared (α = 0.05).

Results

The median trueness was 24.45, 43.45 and 28.70 μm for group PG, IOS and CNV; Group PG gave more accurate trueness than group IOS (P < 0.001) and group CNV (P = 0.033), group CNV showed more accurate trueness than group IOS (P = 0.033). The median precision was 2.00, 36.00 and 29.40 μm for group PG, IOS and CNV; Group PG gave more accurate precision than group IOS (P < 0.001) and group CNV (P < 0.001), group CNV showed more accurate precision than IOS (P = 0.002).

Conclusions

For complete-arch implant rehabilitation, the photogrammetry system showed the best accuracy of all the impression techniques evaluated, followed by the conventional impression technique, and the intraoral scanner provided the least accuracy.
DISE/6mer seed toxicity-a powerful anti-cancer mechanism with implications for other diseases
Authors: Haluck-Kangas Ashley , Patel Monal , Paudel Bidur , Vaidyanathan Aparajitha , Murmann Andrea E. , Peter Marcus E.
Published: December 2021

micro(mi)RNAs are short noncoding RNAs that through their seed sequence (pos. 2–7/8 of the guide strand) regulate cell function by targeting complementary sequences (seed matches) located mostly in the 3′ untranslated region (3′ UTR) of mRNAs. Any short RNA that enters the RNA induced silencing complex (RISC) can kill cells through miRNA-like RNA interference when its 6mer seed sequence (pos. 2–7 of the guide strand) has a G-rich nucleotide composition. G-rich seeds mediate 6mer Seed Toxicity by targeting C-rich seed matches in the 3′ UTR of genes critical for cell survival. The resulting Death Induced by Survival gene Elimination (DISE) predominantly affects cancer cells but may contribute to cell death in other disease contexts. This review summarizes recent findings on the role of DISE/6mer Seed Tox in cancer; its therapeutic potential; its contribution to therapy resistance; its selectivity, and why normal cells are protected. In addition, we explore the connection between 6mer Seed Toxicity and aging in relation to cancer and certain neurodegenerative diseases.
Proposed protocol for treatment of severe periodontitis without platelet transfusion in patients with aplastic anemia: a case report
Authors: Morikawa Satoru , Watanabe Kazuya , Usuda Satoshi , Miyashita Yoko , Nakagawa Taneaki
Published: December 2021

Background

Aplastic anemia is an intractable disease characterized by pancytopenia, susceptibility to infection, and difficulty in achieving hemostasis. In patients with severe periodontal disease and aplastic anemia, spontaneous bleeding from the gingival tissue due to thrombocytopenia and during brushing is common, which may further exacerbate dental issues. Comprehensive periodontal treatment for patients with aplastic anemia is highly challenging and requires collaboration with a hematologist. Here, we discuss the case of a patient with aplastic anemia and severe periodontitis who was successfully treated in collaboration with our hematology department.

Case presentation

A 36-year-old Japanese woman with chief complaints of spontaneous gingival bleeding, pain, and increasing tooth mobility consulted our department. She had developed pancytopenia at age 11 years and was later diagnosed with aplastic anemia, making her susceptible to infection due to leukopenia. The results of the initial periodontal examination led to a diagnosis of severe generalized periodontitis (generalized stage IV grade C periodontitis) caused by leukopenia and poor oral hygiene. We adopted a comprehensive treatment plan, including invasive dental procedures. The patient exhibited no postoperative bleeding due to aplastic anemia-induced thrombocytopenia and experienced a good outcome.

Conclusions

Both physicians and dentists should be aware that immunocompromised patients with aplastic anemia are at risk of developing severe periodontitis with severe alveolar bone resorption if the condition is combined with poor oral hygiene. Even in the presence of aplastic anemia, patients with severe periodontitis can undergo comprehensive dental treatment, including dental extraction and periodontal surgery, if bleeding and susceptibility to infection are controlled. This requires the cooperation of the patient and hematologists and can ultimately contribute to improving the patient’s quality of life.
Plasma glial fibrillary acidic protein and neurofilament light chain for the diagnostic and prognostic evaluation of frontotemporal dementia
Authors: Zhu Nuole , Santos-Santos Miguel , Illán-Gala Ignacio , Montal Victor , Estellés Teresa , Barroeta Isabel , Altuna Miren , Arranz Javier , Muñoz Laia , Belbin Olivia , Sala Isabel , Sánchez-Saudinós Maria Belén , Subirana Andrea , Videla Laura , Pegueroles Jordi , Blesa Rafael , Clarimón Jordi , Carmona-Iragui Maria , Fortea Juan , Lleó Alberto , Alcolea Daniel
Published: December 2021

Background

Astrocytes play an essential role in neuroinflammation and are involved in the pathogenesis of neurodenegerative diseases. Studies of glial fibrillary acidic protein (GFAP), an astrocytic damage marker, may help advance our understanding of different neurodegenerative diseases. In this study, we investigated the diagnostic performance of plasma GFAP (pGFAP), plasma neurofilament light chain (pNfL) and their combination for frontotemporal dementia (FTD) and Alzheimer’s disease (AD) and their clinical utility in predicting disease progression.

Methods

pGFAP and pNfL concentrations were measured in 72 FTD, 56 AD and 83 cognitively normal (CN) participants using the Single Molecule Array technology. Of the 211 participants, 199 underwent cerebrospinal (CSF) analysis and 122 had magnetic resonance imaging. We compared cross-sectional biomarker levels between groups, studied their diagnostic performance and assessed correlation between CSF biomarkers, cognitive performance and cortical thickness. The prognostic performance was investigated, analyzing cognitive decline  through group comparisons by tertile.

Results

Unlike pNfL, which was increased similarly in both clinical groups, pGFAP was increased in FTD but lower than in AD (all P < 0.01). Combination of both plasma markers improved the diagnostic performance to discriminate FTD from AD (area under the curve [AUC]: combination 0.78; pGFAP 0.7; pNfL 0.61, all P < 0.05). In FTD, pGFAP correlated with cognition, CSF and plasma NfL, and cortical thickness (all P < 0.05). The higher tertile of pGFAP was associated with greater change in MMSE score and poor cognitive outcome during follow-up both in FTD (1.40 points annually, hazard ratio [HR] 3.82, P < 0.005) and in AD (1.20 points annually, HR 2.26, P < 0.005).

Conclusions

pGFAP and pNfL levels differ in FTD and AD, and their combination is useful for distinguishing between the two diseases. pGFAP could also be used to track disease severity and predict greater cognitive decline during follow-up in patients with FTD.
Surface environment of Phobos and Phobos simulant UTPS
Authors: Miyamoto Hideaki , Niihara Takafumi , Wada Koji , Ogawa Kazunori , Senshu Hiroki , Michel Patrick , Kikuchi Hiroshi , Hemmi Ryodo , Nakamura Tomoki , Nakamura Akiko M. , Hirata Naoyuki , Sasaki Sho , Asphaug Erik , Britt Daniel T. , Abell Paul A. , Ballouz Ronald-Louis , Banouin Olivier S. , Baresi Nicola , Barucci Maria A. , Biele Jens , Grott Matthias , Hino Hideitsu , Hong Peng K. , Imada Takane , Kameda Shingo , Kobayashi Makito , Libourel Guy , Mogi Katsuro , Murdoch Naomi , Nishio Yuki , Okamoto Shogo , Ota Yuichiro , Otsuki Masatsugu , Otto Katharina A. , Sakatani Naoya , Shimizu Yuta , Takemura Tomohiro , Terada Naoki , Tsukamoto Masafumi , Usui Tomohiro , Willner Konrad
Published: December 2021

The Martian Moons eXploration (MMX) mission will study the Martian moons Phobos and Deimos, Mars, and their environments. The mission scenario includes both landing on the surface of Phobos to collect samples and deploying a small rover for in situ observations. Engineering safeties and scientific planning for these operations require appropriate evaluations of the surface environment of Phobos. Thus, the mission team organized the Landing Operation Working Team (LOWT) and Surface Science and Geology Sub-Science Team (SSG-SST), whose view of the Phobos environment is summarized in this paper. While orbital and large-scale characteristics of Phobos are relatively well known, characteristics of the surface regolith, including the particle size-distributions, the packing density, and the mechanical properties, are difficult to constrain. Therefore, we developed several types of simulated soil materials (simulant), such as UTPS-TB (University of Tokyo Phobos Simulant, Tagish Lake based), UTPS-IB (Impact-hypothesis based), and UTPS-S (Simpler version) for engineering and scientific evaluation experiments.
Small-scale topographic irregularities on Phobos: image and numerical analyses for MMX mission
Authors: Takemura Tomohiro , Miyamoto Hideaki , Hemmi Ryodo , Niihara Takafumi , Michel Patrick
Published: December 2021

The mothership of the Martian Moons eXploration (MMX) will perform the first landing and sampling on the surface of Phobos. For the safe landing, the 2.1-m-wide mothership of the MMX should find a smooth surface with at most 40 cm topographic irregularity, however, whose abundance or even existence is not guaranteed based on current knowledge. We studied the highest resolution (a few meters per pixel) images of Phobos for possible topographic irregularities in terms of boulder (positive relief feature) and crater distributions. We find that the spatial number densities of positive relief features and craters can vary significantly, indicating that the surface irregularities vary significantly over the entire surface. We extrapolate the size-frequency distributions of positive relief features to evaluate the surface roughness below the image resolution limit. We find that the probabilities that topographic irregularities are  < 40 cm for the areas of 4 × 4 m and 20 × 20 m are  > 33% and  < 1% for boulder-rich areas and  > 88% and  > 13% for boulder-poor areas, respectively, even for the worst-case estimates. The estimated probabilities largely increase when we reduce the assumed number of positive relief features, which are more realistic cases. These indicate high probabilities of finding a smooth enough place to land on Phobos’ surface safely.

Graphical Abstract
Deciphering the ChitoCode: fungal chitins and chitosans as functional biopolymers
Authors: Cord-Landwehr Stefan , Moerschbacher Bruno M.
Published: December 2021

Chitins and chitosans are among the most widespread and versatile functional biopolymers, with interesting biological activities and superior material properties. While chitins are evolutionary ancient and present in many eukaryotes except for higher plants and mammals, the natural distribution of chitosans, i.e. extensively deacetylated derivatives of chitin, is more limited. Unequivocal evidence for its presence is only available for fungi where chitosans are produced from chitin by the action of chitin deacetylases. However, neither the structural details such as fraction and pattern of acetylation nor the physiological roles of natural chitosans are known at present. We hypothesise that the chitin deacetylases are generating chitins and chitosans with specific acetylation patterns and that these provide information for the interaction with specific chitin- and chitosan-binding proteins. These may be structural proteins involved in the assembly of the complex chitin- and chitosan-containing matrices such as fungal cell walls and insect cuticles, chitin- and chitosan-modifying and -degrading enzymes such as chitin deacetylases, chitinases, and chitosanases, but also chitin- and chitosan-recognising receptors of the innate immune systems of plants, animals, and humans. The acetylation pattern, thus, may constitute a kind of ‘ChitoCode’, and we are convinced that new in silico, in vitro, and in situ analytical tools as well as new synthetic methods of enzyme biotechnology and organic synthesis are currently offering an unprecedented opportunity to decipher this code. We anticipate a deeper understanding of the biology of chitin- and chitosan-containing matrices, including their synthesis, assembly, mineralisation, degradation, and perception. This in turn will improve chitin and chitosan biotechnology and the development of reliable chitin- and chitosan-based products and applications, e.g. in medicine and agriculture, food and feed sciences, as well as cosmetics and material sciences.
Risk factors for musculoskeletal injuries in the military: a qualitative systematic review of the literature from the past two decades and a new prioritizing injury model
Authors: Sammito Stefan , Hadzic Vedran , Karakolis Thomas , Kelly Karen R. , Proctor Susan P. , Stepens Ainars , White Graham , Zimmermann Wes O.
Published: December 2021

Background

Musculoskeletal injuries (MSkIs) are a leading cause of health care utilization, as well as limited duty and disability in the US military and other armed forces. MSkIs affect members of the military during initial training, operational training, and deployment and have a direct negative impact on overall troop readiness. Currently, a systematic overview of all risk factors for MSkIs in the military is not available.

Methods

A systematic literature search was carried out using the PubMed, Ovid/Medline, and Web of Science databases from January 1, 2000 to September 10, 2019. Additionally, a reference list scan was performed (using the “snowball method”). Thereafter, an international, multidisciplinary expert panel scored the level of evidence per risk factor, and a classification of modifiable/non-modifiable was made.

Results

In total, 176 original papers and 3 meta-analyses were included in the review. A list of 57 reported potential risk factors was formed. For 21 risk factors, the level of evidence was considered moderate or strong. Based on this literature review and an in-depth analysis, the expert panel developed a model to display the most relevant risk factors identified, introducing the idea of the “order of importance” and including concepts that are modifiable/non-modifiable, as well as extrinsic/intrinsic risk factors.

Conclusions

This is the qualitative systematic review of studies on risk factors for MSkIs in the military that has attempted to be all-inclusive. A total of 57 different potential risk factors were identified, and a new, prioritizing injury model was developed. This model may help us to understand risk factors that can be addressed, and in which order they should be prioritized when planning intervention strategies within military groups.
Is greater public transport use associated with higher levels of physical activity in a regional setting? Findings from a pilot study
Authors: Ragaini Bruna S. , Sharman Melanie J. , Lyth Anna , Jose Kim A. , Blizzard Leigh , Peterson Corey , Johnston Fay H. , Palmer Andrew , Williams Julie , Marshall Elaine A. , Morse Megan , Cleland Verity J.
Published: December 2021

Background

Public transport users often accumulate more physical activity than motor vehicle users, but most studies have been conducted in large metropolitan areas with multiple public transport options with limited knowledge of the relationship in regional and rural areas. In a regional city, this pilot study aimed to (1) test the feasibility of preliminary hypotheses to inform future research, (2) test the utility of survey items, and (3) establish stakeholder engagement.

Methods

Data were collected via a cross-sectional online survey of 743 Tasmanian adults. Physical activity outcomes were walking (min/week), total moderate- to vigorous-intensity physical activity (min/week) and attainment of physical activity guidelines (yes/no). Transport variables were frequency of public and private transport use per week. Truncated and log binomial regression examined associations between public/private transport use and physical activity.

Results

Neither frequency of public nor private transport use was associated with minutes of walking (public transport: B − 24.4, 95% CI: − 110.7, 61.9; private transport: B − 1.1, 95% CI: − 72.4, 70.1), minutes of total physical activity (public transport: B − 90.8, 95% CI: − 310.0, 128.5; private transport: B 0.4, 95% CI: − 134.0, 134.9) or not meeting physical activity guidelines (public transport: RR 1.02, 95%CI: 0.95, 1.09; private transport: RR 1.02, 95%CI: 0.96, 1.08).

Conclusions

The hypothesis that public transport users would be more physically active than private transport users was not supported in this pilot study. Stakeholders were engaged and involved in various phases of the research including development of research questions, participant recruitment, and interpretation of findings. Further studies using representative samples and refined measures are warranted to confirm or refute findings.
Response Rate, Event-Free Survival, and Overall Survival in Newly Diagnosed Acute Myeloid Leukemia: US Food and Drug Administration Trial-Level and Patient-Level Analyses
Authors: Norsworthy Kelly J. , Gao Xin , Ko Chia-Wen , Pulte E. Dianne , Zhou Jiaxi , Gong Yutao , Shen Yuan Li , Vallejo Jonathon , Gwise Thomas E. , Sridhara Rajeshwari , Deisseroth Albert B. , Farrell Ann T. , de Claro R. Angelo , Blumenthal Gideon M. , Pazdur Richard
Published: December 2021

PURPOSE

To explore trial-level and patient-level associations between response (complete remission [CR] and CR + CR with incomplete hematologic [CRi] or platelet [CRp] recovery), event-free survival (EFS), and overall survival (OS) in newly diagnosed acute myeloid leukemia (AML) trials of intensive chemotherapy.

METHODS

We identified data from eight randomized, active-controlled trials of intensive chemotherapy submitted to the US Food and Drug Administration for treatment of newly diagnosed AML (N = 4,482). Associations between trial-level odds ratios (ORs) for CR and CR + CRi or CRp, and hazard ratios (HRs) for EFS and OS were analyzed using weighted linear regression models. We performed patient-level responder analyses to compare OS by response using pooled data from all studies.

RESULTS

In trial-level analyses, association between HR for OS and OR for CR was moderate (R2 = 0.49; 95% CI, 0.05 to 0.86), as was the association with OR for CR + CRi or CRp (R2 = 0.48; 95% CI, 0.05 to 0.99). For OS versus EFS, a strong association was observed (R2 = 0.87; 95% CI, 0.47 to 0.98) when EFS definitions were harmonized across trials using raw data. In the patient-level responder analyses, patients who achieved CR had better OS compared with CRi or CRp responders (0.73; 95% CI, 0.64 to 0.84) and nonresponders (HR, 0.33; 95% CI, 0.31 to 0.37).

CONCLUSION

On a trial level, there is a moderate association between OS and CR rate. A strong association between EFS and OS was observed. However, CIs were wide, and results became moderate using alternative definitions for EFS. Patient-level analyses showed CR responders have better OS compared with CRi or CRp responders and nonresponders. A therapy in newly diagnosed AML with benefit in EFS or substantial benefit in CR rate would be likely to have an OS effect.