bluuebunny/crossref_metadata_2025 huggingface dataset:
An Online Application for Retinoblastoma Surveillance
Authors: Singh Nakul , DeBenedictis Meghan J. , Singh Arun D.
Published: March 2020

Background: Retinoblastoma (RB) is a potentially heritable childhood cancer that is vision- and life-threatening. Assessing the risk of inheriting RB is important for structuring ophthalmic and genetic screening of family members. Purpose: To create a free online application that integrates phenotypic, genetic, and familial relationships with clinical best practice surveillance guidelines for families with RB. Methods: The risk of germline RB1 gene mutation was assessed for first- and second-degree relatives of a proband under variable clinical scenarios, integrating age, phenotype, relationship data, and genotype (germline RB1 mutation status: detected, undetected, not tested). Based on the assessed risk of a germline RB1 mutation, recommendations regarding further genetic testing as well as ophthalmic surveillance were derived from consensus guidelines. Results: The recommendations depend on the RB1 germline mutation status (detected, undetected, not tested), which were further subcategorized by the results of tumor phenotype, relationship to proband, age of the relative, and family structure. The online application is available at https://nakul-singh.shinyapps.io/RB_Screening_rec/. Conclusions: The assessed risk of germline RB1 mutation determines ophthalmic surveillance recommendations. The tool may have most value in regions where access to specialized care is limited.
Impact of Preoperative Magnetic Resonance Imaging Anatomic Features on Urinary Continence Recovery after Laparoscopic Radical Prostatectomy
Authors: Yang Bin , Zhang Fan , Xiao Chunlei , Lu Jian , Ma Lulin , Huang Yi
Published: March 2020

Purpose: To evaluate the impact of preoperative magnetic resonance imaging anatomic features on urinary continence recovery after laparoscopic radical prostatectomy (LRP). Methods: We retrospectively analyzed 150 consecutive prostate cancer patients who underwent LRP between July 2015 and June 2018 in our institution. Patients reporting freedom from using safety pad (0 pads/day) were defined as urinary continent. We evaluated the association of urinary continence recovery after LRP and the perioperative variables, including age, prostatic volume (PV), intravesical prostatic protrusion length (IPPL), membranous urethral length (MUL), and neurovascular bundle (NVB) sparing status. Kaplan-Meier and log-rank tests were used to compare urinary continence rates between groups. Univariate and multivariate Cox proportional hazards regression analyses were used to identify independent predictors for urinary continence recovery. Results: 60.6% (91/150), 83.3% (125/150), and 96.0% (144/150) of the patients experienced urinary continence recovery at 3, 6, and 12 months, respectively. There was significant difference in PV, IPPL, MUL, and NVB sparing between groups stratified by urinary continence status at 3, 6, and 12 months. Kaplan-Meier curves of urinary continence rates showed significant differences between groups stratified by PV (<50 mL vs. ≥50 mL, p < 0.001), IPPL (<5 mm vs. ≥5 mm, p < 0.001), MUL (≥15 mm vs. <15 mm, p < 0.001), and NVB sparing status (yes vs. no, p = 0.003), respectively. On univariate analysis, PV, IPPL, MUL, and NVB sparing were significantly associated with urinary continence recovery (all, p < 0.05). On multivariate analysis, only IPPL (HR = 0.94, p = 0.003) and MUL (HR = 1.10, p < 0.001) were independent predictors for urinary continence recovery. Conclusion: Patients with larger IPPL and shorter MUL have higher chances of delayed recovery of urinary continence after LRP. IPPL and MUL were reliable morphometric parameters for predicting urinary continence.
Kidney Health for Everyone Everywhere – From Prevention to Detection and Equitable Access to Care
Authors: Li Philip Kam-Tao , Garcia-Garcia Guillermo , Lui Siu-Fai , Andreoli Sharon , Fung Winston Wing-Shing , Hradsky Anne , Kumaraswami Latha , Liakopoulos Vassilios , Rakhimova Ziyoda , Saadi Gamal , Strani Luisa , Ulasi Ifeoma , Kalantar-Zadeh Kamyar ,   for the World Kidney Day Steering Committee
Published: March 2020

The global burden of chronic kidney disease (CKD) is rapidly increasing with a projection of becoming the 5th most common cause of years of life lost globally by 2040. Aggravatingly, CKD is a major cause of catastrophic health expenditure. The costs of dialysis and transplantation consume up to 3% of the annual healthcare budget in high-income countries. Crucially, however, the onset and progression of CKD is often preventable. In 2020, the World Kidney Day campaign highlights the importance of preventive interventions – be it primary, secondary or tertiary. This complementing article focuses on outlining and analyzing measures that can be implemented in every country to promote and advance CKD prevention. Primary prevention of kidney disease should focus on the modification of risk factors and addressing structural abnormalities of the kidney and urinary tracts, as well as exposure to environmental risk factors and nephrotoxins. In persons with pre-existing kidney disease, secondary prevention, including blood pressure optimization and glycemic control, should be the main goal of education and clinical interventions. In patients with advanced CKD, management of co-morbidities such as uremia and cardiovascular disease is a highly recommended preventative intervention to avoid or delay dialysis or kidney transplantation. Political efforts are needed to proliferate the preventive approach. While national policies and strategies for non-communicable diseases might be present in a country, specific policies directed toward education and awareness about CKD screening, management and treatment are often lacking. Hence, there is an urgent need to increase the awareness of the importance of preventive measures throughout populations, professionals and policy makers.
Hemophagocytic Lymphohistiocytosis and Inflammatory Bowel Disease: Case Report and Systematic Review
Authors: Brambilla Bárbara , Barbosa Amanda Machado , Scholze Cassiano da Silva , Riva Floriano , Freitas Lislene , Balbinot Raul Angelo , Balbinot Silvana , Soldera Jonathan
Published: March 2020

Aim: To report a case of a female patient with hemophagocytic lymphohistiocytosis (HLH) and to systematically review the available cases of the association between HLH and inflammatory bowel disease (IBD). Methods: In accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, retrieval of studies was based on Medical Subject Headings and Health Sciences Descriptors, which were combined using Boolean operators. Searches were run on the electronic databases Scopus, Web of Science, MEDLINE (PubMed), Biblioteca Regional de Medicina, Latin American and Caribbean Health Sciences Literature, Cochrane Library for Systematic Reviews and Opengrey.eu. Languages were restricted to English, Spanish and Portuguese. There was no date of publication restrictions. The reference lists of the studies retrieved were searched manually. Results: The search strategy retrieved 223 references. In the final analysis, 28 references were included, with the report of 35 cases. The most common clinical finding was fever, 57% of patients had a cytomegalovirus infection and 30 patients were on thiopurines previously to HLH diagnosis. Most patients were treated with steroids and antiviral therapy. All-cause mortality was 22%. Conclusion: These findings suggest that there might be a connection of HLH to IBD, opportunistic viral infections and the use of thiopurines. Due to the severity of such disease, the clinical suspicion is paramount to early diagnosis and therapy.
Treatment Outcomes of Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitis in Patients Over Age 75 Years: A Meta-Analysis
Authors: Morris Adam D. , Elsayed Mohamed E. , Ponnusamy Arvind , Rowbottom Anthony , Martin Francis , Geetha Duvuru , Dhaygude Ajay P.
Published: March 2020

Background: The benefits of treating anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV) in advancing age remains unclear with most published studies defining elderly as ≥65 years. This study aims to determine outcomes of induction immunosuppression in patients aged ≥75 years. Methods: A cohort of patients aged ≥75 years with a diagnosis of AAV between 2006 and 2018 was constructed from 2 centres. Follow-up was to 2 years or death. Analysis included multivariable Cox regression to compare mortality and end-stage renal disease (ESRD) based on receipt of induction immunosuppression therapy with either cyclophosphamide or rituximab. A systematic review of outcome studies was subsequently undertaken amongst this patient group through Pubmed, Cochrane and Embase databases from inception until October 16, 2019. Results: Sixty-seven patients were identified. Mean age was 79 ± 2.9 years and 82% (n = 55) received induction immunosuppression. Following systematic review, 4 studies were eligible for inclusion, yielding a combined total of 290 patients inclusive of our cohort. The aggregated 1-year mortality irrespective of treatment was 31% (95% CI 25–36%). Within our cohort, induction immunosuppression therapy was associated with a significantly lower 2-year mortality risk (hazard ratio [HR] 0.29 [95% CI 0.09–0.93]). The pooled HR by meta-analysis confirmed this with a significant risk reduction for death (HR 0.31 [95% CI 0.16–0.57], I2 = 0%). Treated patients had a lower pooled rate of ESRD, but was not statistically significant (HR 0.71 [95% CI 0.15–3.35]). Conclusion: This meta-analysis suggests that patients ≥75 years with AAV do benefit from induction immunosuppression with a significant survival benefit. Age alone should not be a limiting factor when considering treatment.
Lysine-Specific Demethylase-1 Deficiency Increases Agonist Signaling Via the Mineralocorticoid Receptor
Authors: Treesaranuwattana Thitinan , Wong Kelly Yin Han , Brooks Danielle L. , Tay Chee Sin , Williams Gordon H. , Williams Jonathan S. , Pojoga Luminita H.
Published: March 2020

LSD1 (lysine-specific demethylase-1) is an epigenetic regulator of gene transcription. LSD1 risk allele in humans and LSD1 deficiency (
LSD1
+/−
) in mice confer increasing salt-sensitivity of blood pressure with age, which evolves into salt-sensitive hypertension in older individuals. However, the mechanism underlying the relationship between LSD1 and salt-sensitivity of blood pressure remains elusive. Here, we show that LSD1 genotype (in humans) and LSD1 deficiency (in mice) lead to similar associations with increased blood pressure and urine potassium levels but with decreased aldosterone levels during a liberal salt diet. Thus, we hypothesized that LSD1 deficiency leads to an MR (mineralocorticoid receptor)-dependent hypertensive state. Yet, further studies in
LSD1
+/−
mice treated with the MR antagonist eplerenone demonstrate that hypertension, kaliuria, and albuminuria are substantially improved, suggesting that the ligand-independent activation of the MR is the underlying cause of this LSD1 deficiency–mediated phenotype. Indeed, while MR and epithelial sodium channel expression levels were increased in
LSD1
+/−
mouse kidney tissues, aldosterone secretion from
LSD1
+/−
glomerulosa cells was significantly lower. Collectively, these data establish that LSD1 deficiency leads to an inappropriate activation and increased levels of the MR during a liberal salt regimen and suggest that inhibiting the MR pathway is a useful strategy for treatment of hypertension in human LSD1 risk allele carriers.
DPP (Dipeptidyl Peptidase)-4 Inhibitor Attenuates Ang II (Angiotensin II)–Induced Cardiac Hypertrophy via GLP (Glucagon-Like Peptide)-1–Dependent Suppression of Nox (Nicotinamide Adenine Dinucleotide Phosphate Oxidase) 4-HDAC (Histone Deacetylase) 4 Pathway
Authors: Okabe Kosuke , Matsushima Shouji , Ikeda Soichiro , Ikeda Masataka , Ishikita Akihito , Tadokoro Tomonori , Enzan Nobuyuki , Yamamoto Taishi , Sada Masashi , Deguchi Hiroko , Shinohara Keisuke , Ide Tomomi , Tsutsui Hiroyuki
Published: March 2020

Nox4 (NADPH [Nicotinamide adenine dinucleotide phosphate] oxidase 4) is a major source of oxidative stress and is intimately involved in cardiac hypertrophy. DPP (Dipeptidyl peptidase)-4 inhibitor has been reported to regulate Nox4 expression in adipose tissues. However, its effects on Nox4 in cardiac hypertrophy are still unclear. We investigated whether DPP-4 inhibitor could ameliorate cardiac hypertrophy by regulating Nox4 and its downstream targets. Ang II (Angiotensin II; 1.44 mg/kg per day) or saline was continuously infused into C57BL/6J mice with or without teneligliptin (a DPP-4 inhibitor, 30 mg/kg per day) in the drinking water for 1 week. Teneligliptin significantly suppressed plasma DPP-4 activity without any significant changing aortic blood pressure or metabolic parameters such as blood glucose and insulin levels. It attenuated Ang II–induced increases in left ventricular wall thickness and the ratio of heart weight to body weight. It also significantly suppressed Ang II–induced increases in Nox4 mRNA, 4-hydroxy-2-nonenal, and phosphorylation of HDAC4 (histone deacetylase 4), a downstream target of Nox4 and a crucial suppressor of cardiac hypertrophy, in the heart. Exendin-3 (150 pmol/kg per minute), a GLP-1 (glucagon-like peptide 1) receptor antagonist, abrogated these inhibitory effects of teneligliptin on Nox4, 4-hydroxy-2-nonenal, phosphorylation of HDAC4, and cardiac hypertrophy. In cultured neonatal cardiomyocytes, exendin-4 (100 nmol/L, 24 hours), a GLP-1 receptor agonist, ameliorated Ang II–induced cardiomyocyte hypertrophy and decreased in Nox4, 4-hydroxy-2-nonenal, and phosphorylation of HDAC4. Furthermore, exendin-4 prevented Ang II–induced decrease in nuclear HDAC4 in cardiomyocytes. In conclusion, GLP-1 receptor stimulation by DPP-4 inhibitor can attenuate Ang II–induced cardiac hypertrophy by suppressing of the Nox4-HDAC4 axis in cardiomyocytes.
Possible Limitations to the Role of Subsequent Agreements and Subsequent Practice – Viewed from Some State Practices
Authors: Hamamoto Yukiya
Published: March 2020

The International Law Commission completed its work on subsequent agreements and subsequent practice in relation to the interpretation of treaties. While acknowledging the importance of the work, this article attempts to highlight some issues that may limit treaty interpretation through subsequent agreements and subsequent practice. Concrete examples of treaties on the avoidance of double taxation and a treaty ending a war are used to illustrate such potential limitations.
Contributions to the Surface Downwelling Longwave Irradiance during Arctic Winter at Utqiaġvik (Barrow), Alaska
Authors: Sokolowsky G. Alexander , Clothiaux Eugene E. , Baggett Cory F. , Lee Sukyoung , Feldstein Steven B. , Eloranta Edwin W. , Cadeddu Maria P. , Bharadwaj Nitin , Johnson Karen L.
Published: March 2020

Intrusions of warm, moist air into the Arctic during winter have emerged as important contributors to Arctic surface warming. Previous studies indicate that temperature, moisture, and hydrometeor enhancements during intrusions all make contributions to surface warming via emission of radiation down to the surface. Here, datasets from instrumentation at the Atmospheric Radiation Measurement User Facility in Utqiaġvik (formerly Barrow) for the six months from November through April for the six winter seasons of 2013/14–2018/19 were used to quantify the atmospheric state. These datasets subsequently served as inputs to compute surface downwelling longwave irradiances via radiative transfer computations at 1-min intervals with different combinations of constituents over the six winter seasons. The computed six winter average irradiance with all constituents included was 205.0 W m−2, close to the average measured irradiance of 206.7 W m−2, a difference of −0.8%. During this period, water vapor was the most important contributor to the irradiance. The computed average irradiance with dry gas was 71.9 W m−2. Separately adding water vapor, liquid, or ice to the dry atmosphere led to average increases of 2.4, 1.8, and 1.6 times the dry atmosphere irradiance, respectively. During the analysis period, 15 episodes of warm, moist air intrusions were identified. During the intrusions, individual contributions from elevated temperature, water vapor, liquid water, and ice water were found to be comparable to each other. These findings indicate that all properties of the atmospheric state must be known in order to quantify the radiation coming down to the Arctic surface during winter.
Use of the Autoregressive Integrated Moving Average (ARIMA) Model to Forecast Near-Term Regional Temperature and Precipitation
Authors: Lai Yuchuan , Dzombak David A.
Published: March 2020

A data-driven approach for obtaining near-term (2–20 years) regional temperature and precipitation projections utilizing local historical observations was established in this study to facilitate civil and environmental engineering applications. Given the unique characteristics of temporal correlation and skewness exhibited in individual time series of temperature and precipitation variables, a statistical time series forecasting technique was developed based on the autoregressive integrated moving average (ARIMA) model. Annual projections obtained from the ARIMA model—depending on individual series—can be interpreted as an integration of the most recent observations and the long-term historical trend. In addition to annual temperature and precipitation forecasts, methods of estimating confidence intervals for different return periods and simulating future daily temperature and precipitation were developed to extend the applicability for use in engineering. Quantitative comparisons of annual temperature and precipitation forecasts developed from the ARIMA model and other common statistical techniques such as a linear trend method were performed. Results suggested that while the ARIMA model cannot outperform all other techniques for all evaluated climate indices, the ARIMA model in general provides more accurate projections—especially interval forecasts—and is more reliable than other common statistical techniques. With the use of the ARIMA-based statistical forecasting model, interpretable and reliable near-term, location-specific temperature and precipitation forecasts can be obtained for consideration of changing climate in civil and environmental engineering applications.
A Theoretical Note on Sector-specific FDI Inflow in Developing Economies and the Real Exchange Rate
Authors: Mandal Biswajit , Bhattacharjee Prasun
Published: March 2020

Using a hybrid of the Heckscher–Ohlin model and specific factor model of trade, this article considers the phenomenon of FDI inflows only in the exportable sector of developing economies. We investigate the impact of such capital flow on factor prices and the real exchange rate (RER) in the host country. Our results indicate that the exportable production expands while both the non-traded good production and the return to the factor specific to the non-traded good decrease, consequent upon an inflow of capital specific to the exportable sector. The effect of such inflow of foreign capital on the RER is unambiguous and it increases.

JEL Codes: F1, F21, F31
The Examination of Instrumental Activities of Daily Living and Perceived Adulthood in Emerging Adults
Authors: Ayotte Brian , Revell Andrew , Belanger Nicole
Published: March 2020

Emerging adults differ in terms of the extent to which they perceive themselves as adults. We examined how the ability to perform activities related to independent living (i.e., instrumental activities of daily living [IADLs]) was associated with perceived adulthood. Data were collected from 236 emerging adults in college. Results suggested that IADL scores were positively related to perceived adulthood and achieved criteria of adulthood even after controlling for race, year in school, age, and sex. Results are discussed in terms of the development and importance of IADLs during emerging adulthood.
Making Sense of Temples and Tirthas: Rajput Construction Under Mughal Rule
Authors: Asher Catherine B.
Published: March 2020

This article examines temple construction under Mughal rule by significant Rajput rulers—some reluctant and some amenable—to accepting Mughal authority. During the sixteenth through eighteenth centuries high ranking Hindu nobles who easily found favour with the Mughal court built on both their ancestral lands and on crown lands, but those who accepted Mughal hegemony under duress had a more complicated attitude towards temple construction. The temples that the latter group provided were largely in their own territories, often at pilgrimage sites or at sites they intended to transform into pilgrimage sites. The main questions which is article addresses are: Where did these rulers build temples, why and what forms did they take? How does temple construction provide insights into cultural and political aspirations of Rajput kingdoms? Finally, what were the problems arising out of neglect associated of their maintenance and upkeep?
‘It's about being safe and free to be who you are’: Exploring the lived experiences of queer migrants, refugees and asylum seekers in South Africa
Authors: Marnell John , Oliveira Elsa , Khan Gabriel Hoosain
Published: March 2020

This article presents findings from three arts-based studies conducted by the African Centre for Migration and Society, in partnerships with Gay and Lesbian Memory in Action and the Sisonke National Sex Worker Movement. Drawing on participant-created visual and narrative artefacts, the article offers insights into the complex ways in which queer migrants, refugees and asylum seekers living in South Africa negotiate their identities, resist oppression and confront stereotypes. It reveals the dynamic ways in which queer migrants, refugees and asylum seekers forge a sense of belonging in spite of concurrent vulnerabilities and structural discrimination. It also reflects on the benefits and limitations of using participatory arts-based research with marginalised groups.
Modelling moisture conditions behind brick veneer cladding: Verification of common approaches by field measurements
Authors: Vanpachtenbeke Michiel , Langmans Jelle , Van den Bulcke Jan , Van Acker Joris , Roels Staf
Published: March 2020

Cavity walls consisting of an outer leaf, a cavity and an inner leaf are a widespread building enclosure configuration because of their good performance regarding rain tightness. To increase the drying potential, open head joints are typically provided in the brick outer leaf, creating cavity ventilation. Even though this cavity ventilation has a limited effect on the drying out of the brick veneer, it can significantly reduce the moisture levels inside the cavity. This might be crucial when the brick veneer is combined with, for example, a wooden load-bearing wall. A reliable prediction of the cavity moisture levels is hence essential. However, previous studies showed that the ventilation rate in the cavity is highly fluctuating in both magnitude and direction. That is why most numerical models simplify cavity ventilation by neglecting it, replacing it by an equivalent resistance, assuming a constant air change rate and so on. This article verifies common assumptions in numerical models to incorporate cavity ventilation behind a brick veneer cladding, by confronting the simulations with detailed field studies. The results showed that for walls exposed to driving rain and solar radiation, most simplified one-dimensional simulations do not suffice to predict the moisture content in the cavity in a reliable way. Only with two-dimensional simulations, incorporating the airflow in the cavity, a good agreement with the in situ measurements was obtained. Furthermore, the two-dimensional models showed to be able to capture the moisture gradient along with the height of the wall rather precisely.
Evolution of retrovirus-infected premalignant T-cell clones prior to adult T-cell leukemia/lymphoma diagnosis
Authors: Rowan Aileen G. , Dillon Richard , Witkover Aviva , Melamed Anat , Demontis Maria-Antonietta , Gillet Nicolas A. , Mun Liew Jun , Bangham Charles R. M. , Cook Lucy B. , Fields Paul A. , Taylor Graham P.
Published: March 2020

Adult T-cell leukemia/lymphoma (ATL) is an aggressive hematological malignancy caused by human T-cell leukemia virus type-1 (HTLV-1). ATL is preceded by decades of chronic HTLV-1 infection, and the tumors carry both somatic mutations and proviral DNA integrated into the tumor genome. In order to gain insight into the oncogenic process, we used targeted sequencing to track the evolution of the malignant clone in 6 individuals, 2 to 10 years before the diagnosis of ATL. Clones of premalignant HTLV-1–infected cells bearing known driver mutations were detected in the blood up to 10 years before individuals developed acute and lymphoma subtype ATL. Six months before diagnosis, the total number and variant allele fraction of mutations increased in the blood. Peripheral blood mononuclear cells from premalignant cases (1 year prediagnosis) had significantly higher mutational burden in genes frequently mutated in ATL than did high-risk, age-matched HTLV-1 carriers who remained ATL-free after a median of 10 years of follow-up. These data show that HTLV-1–infected T-cell clones carrying key oncogenic driver mutations can be detected in cases of ATL years before the onset of symptoms. Early detection of such mutations may enable earlier and more effective intervention to prevent the development of ATL.
Clinicopathologic predictors of renal outcomes in light chain cast nephropathy: a multicenter retrospective study
Authors: Royal Virginie , Leung Nelson , Troyanov Stéphan , Nasr Samih H. , Écotière Laure , LeBlanc Richard , Adam Benjamin A. , Angioi Andrea , Alexander Mariam P. , Asunis Anna Maria , Barreca Antonella , Bianco Paola , Cohen Camille , Drosou Maria E. , Fatima Huma , Fenoglio Roberta , Gougeon François , Goujon Jean-Michel , Herrera Guillermo A. , Knebelmann Bertrand , Lepori Nicola , Maletta Francesca , Manso Rita , Motwani Shveta S. , Pani Antonello , Rabant Marion , Rennke Helmut G. , Rocatello Dario , Rosenblum Frida , Sanders Paul W. , Santos Afonso , Soto Karina , Sis Banu , Touchard Guy , Venner Christopher P. , Bridoux Frank
Published: March 2020

Light chain cast nephropathy (LCCN) in multiple myeloma often leads to severe and poorly reversible acute kidney injury. Severe renal impairment influences the allocation of chemotherapy and its tolerability; it also affects patient survival. Whether renal biopsy findings add to the clinical assessment in predicting renal and patient outcomes in LCCN is uncertain. We retrospectively reviewed clinical presentation, chemotherapy regimens, hematologic response, and renal and patient outcomes in 178 patients with biopsy-proven LCCN from 10 centers in Europe and North America. A detailed pathology review, including assessment of the extent of cast formation, was performed to study correlations with initial presentation and outcomes. Patients presented with a mean estimated glomerular filtration rate (eGFR) of 13 ± 11 mL/min/1.73 m2, and 82% had stage 3 acute kidney injury. The mean number of casts was 3.2/mm2 in the cortex. Tubulointerstitial lesions were frequent: acute tubular injury (94%), tubulitis (82%), tubular rupture (62%), giant cell reaction (60%), and cortical and medullary inflammation (95% and 75%, respectively). Medullary inflammation, giant cell reaction, and the extent of cast formation correlated with eGFR value at LCCN diagnosis. During a median follow-up of 22 months, mean eGFR increased to 43 ± 30 mL/min/1.73 m2. Age, β2-microglobulin, best hematologic response, number of cortical casts per square millimeter, and degree of interstitial fibrosis/tubular atrophy (IFTA) were independently associated with a higher eGFR during follow-up. This eGFR value correlated with overall survival, independently of the hematologic response. This study shows that extent of cast formation and IFTA in LCCN predicts the quality of renal response, which, in turn, is associated with overall survival.
Nonpermissive bone marrow environment impairs early B-cell development in common variable immunodeficiency
Authors: Troilo Arianna , Wehr Claudia , Janowska Iga , Venhoff Nils , Thiel Jens , Rawluk Justyna , Frede Natalie , Staniek Julian , Lorenzetti Raquel , Schleyer Marei-Theresa , Herget Georg W. , Konstantinidis Lukas , Erlacher Miriam , Proietti Michele , Camacho-Ordonez Nadezhda , Voll Reinhard Edmund , Grimbacher Bodo , Warnatz Klaus , Salzer Ulrich , Rizzi Marta
Published: March 2020

Common variable immunodeficiency (CVID) is a disease characterized by increased susceptibility to infections, hypogammaglobulinemia, and immune dysregulation. Although CVID is thought to be a disorder of the peripheral B-cell compartment, in 25% of patients, early B-cell development in the bone marrow is impaired. Because poor B-cell reconstitution after hematopoietic stem cell transplantation has been observed, we hypothesized that in some patients the bone marrow environment is not permissive to B-cell development. Studying the differentiation dynamics of bone marrow-derived CD34+ cells into immature B cells in vitro allowed us to distinguish patients with B-cell intrinsic defects and patients with a nonpermissive bone marrow environment. In the former, immature B cells did not develop and in the latter CD34+ cells differentiated into immature cells in vitro, but less efficiently in vivo. In a further group of patients, the uncommitted precursors were unable to support the constant development of B cells in vitro, indicating a possible low frequency or exhaustion of the precursor population. Hematopoietic stem cell transplantation would result in normal B-cell repopulation in case of intrinsic B-cell defect, but in defective B-cell repopulation in a nonpermissive environment. Our study points to the importance of the bone marrow niche in the pathogenesis of CVID.
Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial
Authors: Jagasia Madan , Perales Miguel-Angel , Schroeder Mark A. , Ali Haris , Shah Nirav N. , Chen Yi-Bin , Fazal Salman , Dawkins Fitzroy W. , Arbushites Michael C. , Tian Chuan , Connelly-Smith Laura , Howell Michael D. , Khoury H. Jean
Published: March 2020

Patients who develop steroid-refractory acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation have poor prognosis, highlighting an unmet therapeutic need. In this open-label phase 2 study (ClinicalTrials.gov identifier: NCT02953678), patients aged at least 12 years with grades II to IV steroid-refractory aGVHD were eligible to receive ruxolitinib orally, starting at 5 mg twice daily plus corticosteroids, until treatment failure, unacceptable toxicity, or death. The primary end point was overall response rate (ORR) at day 28; the key secondary end point was duration of response (DOR) at 6 months. As of 2 July 2018, 71 patients received at least 1 dose of ruxolitinib. Forty-eight of those patients (67.6%) had grade III/IV aGVHD at enrollment. At day 28, 39 patients (54.9%; 95% confidence interval, 42.7%-66.8%) had an overall response, including 19 (26.8%) with complete responses. Best ORR at any time was 73.2% (complete response, 56.3%). Responses were observed across skin (61.1%), upper (45.5%) and lower (46.0%) gastrointestinal tract, and liver (26.7%). Median DOR was 345 days. Overall survival estimate at 6 months was 51.0%. At day 28, 24 (55.8%) of 43 patients receiving ruxolitinib and corticosteroids had a 50% or greater corticosteroid dose reduction from baseline. The most common treatment-emergent adverse events were anemia (64.8%), thrombocytopenia (62.0%), hypokalemia (49.3%), neutropenia (47.9%), and peripheral edema (45.1%). Ruxolitinib produced durable responses and encouraging survival compared with historical data in patients with steroid-refractory aGVHD who otherwise have dismal outcomes. The safety profile was consistent with expectations for ruxolitinib and this patient population.
Midgut microbiota diversity of potato tuber moth associated with potato tissue consumed
Authors: Zheng Yaqiang , Xiao Guanli , Zhou Wenwu , Gao Yulin , Li Zhengyue , Du Guangzu , Chen Bin
Published: March 2020

Background

The potato tuber moth (PTM), Phthorimaea operculella (Zeller), is a worldwide pest that feeds on both the leaves and tubers of potato plants. PTM larvae can digest leaves, or tubers, resulting in serious damage to potato plants in the field and potato tubers in storage. To understand how midgut bacterial diversity is influenced by the consumption of these two tissue types, the symbiotic bacteria in the potato-feeding PTM midgut and the endophytic bacteria of potato tissues were analyzed.

Results

At the genus level, the bacterial community composition in the PTM midgut was influenced by the tissues consumed, owing to their different nutrient contents. Escherichia_Shigella and Enterobacter were the most dominant genera in the midgut of leaf-feeding and tuber-feeding PTMs, respectively. Interestingly, even though only present in low abundance in leaves and tubers, Escherichia_Shigella were dominantly distributed only in the midgut of leaf-feeding PTMs, indicating that specific accumulation of these genera have occurred by feeding on leaves. Moreover, Enterobacter, the most dominant genus in the midgut of tuber-feeding PTMs, was undetectable in all potato tissues, indicating it is gut-specific origin and tuber feeding-specific accumulation. Both Escherichia_Shigella and Enterobacter abundances were positively correlated with the dominant contents of potato leaves and tubers, respectively.

Conclusions

Enrichment of specific PTM midgut bacterial communities was related to different nutrient levels in different tissues consumed by the insect, which in turn influenced host utilization. We provide evidence that a portion of the intestinal microbes of PTMs may be derived from potato endophytic bacteria and improve the understanding of the relationship between potato endophytic bacteria and the gut microbiota of PTMs, which may offer support for integrated management of this worldwide pest.
Heparin-binding protein measurement improves the prediction of myocardial injury-related cardiogenic shock
Authors: Pan Tuo , Long Guang-Feng , Chen Cheng , Zhang Hai-Tao , Wang Jun-Xia , Ahaskar Anshu , Chen Hong-Bing , Wang Dong-Jin
Published: March 2020

Background

Heparin-binding protein (HBP), a potent inducer of increased vascular permeability, is a potentially useful biomarker for predicting outcomes in patients with postoperative myocardial injury-related cardiogenic shock (MIRCS). We aimed to evaluate and validate HBP as a prognostic biomarker for postoperative MIRCS.

Methods

We performed a case-control study in 792 patients undergoing cardiac surgery from January 1, 2016, to August 1, 2019, including 172 patients with postoperative MIRCS and 620 age- and sex-matched controls. The association between HBP and MIRCS was determined by multivariate logistic regression analysis. Receiver operating characteristic curves (ROCs) with area under the curve (AUC) were performed to calculate the cut-off value, sensitivity and specificity. The association between HBP and cardiac troponin T (cTnT) was determined by multivariable linear regression analysis. Blood samples were drawn from the coronary sinus and arterial line of the cardiopulmonary bypass (CPB) before aortic cross-clamping (time point 1) and 5 min after aortic declamping (time point 2).

Results

Before aortic cross-clamping, coronary sinus HBP (HBPCS1) showed no differences between the two groups. However, after declamping, the MIRCS group had a significantly higher sinus HBP level (HBPCS2) than did the control group. HBPCS2 predicted MIRCS with an AUC of 0.85 (95% CI: 0.81–0.89, cut-off: 220 ng/ml, sensitivity: 92% and specificity: 70%). After adjusting for confounding factors, we found that HBP was an independent risk factor for MIRCS (OR: 7.65, 95% CI: 4.86–12.06, P < 0.01) and was positively associated with cTnT (β > 0, P < 0.01).

Conclusions

Elevated levels of coronary sinus HBP were useful biomarkers for predicting MIRCS after cardiac surgery.
Association between serum liver enzymes and hypertension: a cross-sectional study in Bangladeshi adults
Authors: Rahman Sadaqur , Islam Shiful , Haque Tangigul , Kathak Rahanuma Raihanu , Ali Nurshad
Published: March 2020

Background

Hypertension is a major contributing factor to cardiovascular disease and is a leading cause of death in the world. The association between hepatic enzymes and hypertension has been reported in limited studies and the findings are inconsistent; data from Bangladeshi adults are not available yet. This study was conducted to estimate the prevalence of elevated liver enzymes and evaluate the association of elevated liver enzymes with hypertension in Bangladeshi adults.

Methods

In this cross-sectional study, 302 blood samples were collected from adult participants and analyzed the serum concentrations of alanine and aspartate aminotransferase (ALT, AST), alkaline phosphatase (ALP), and γ-glutamyltransferase (GGT) and other markers related to hypertension. Hypertension was defined as resting SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg. Associations between elevated liver enzymes and hypertension were evaluated by multinomial logistic regression.

Results

The mean concentrations of serum ALT, AST and GGT were significantly higher in the hypertensive group compared to the normotensive group (p < 0.01, p < 0.01 and p < 0.001, respectively). Overall, 49.2% of subjects in the hypertensive group and 38.1% of individuals in the normotensive group had at least one or more elevated liver enzymes. The prevalence of elevated ALT, AST, and GGT was significantly higher among participants in the hypertensive group compared to the normotensive group (p < 0.01, p < 0.01 and p < 0.001, respectively). An increasing trend for elevated liver enzymes was observed with increasing blood pressure. Serum ALT and GGT showed an independent relationship with hypertension.

Conclusions

The prevalence of elevated liver enzymes was higher in hypertensive individuals. Increased serum ALT and GGT activities were positively associated with hypertension in Bangladeshi adults.
Continuous renal replacement therapy in patients with HIV/AIDS
Authors: Guo Hebing , Liu Jingyuan , Pu Lin , Hao Jingjing , Yin Ningning , Liu Yufeng , Xiong Haofeng , Li Ang
Published: March 2020

Background

Acute kidney injury (AKI) is a common complication among human immunodeficiency virus (HIV)-infected patients resulting in increased morbidity and mortality. Continuous renal replacement therapy (CRRT) is a useful method and instrument in critically ill patients with fluid overload and metabolic disarray, especially in those who are unable to tolerate the intermittent hemodialysis. However, the epidemiology, influence factors of CRRT and mortality in patients with HIV/AIDS are still unclear in China. This study aims to study the HIV-infected patients admitted in Intensive Care Unit (ICU) and explore the influence factors correlated with CRRT and their prognosis.

Methods

We performed a retrospective case-control study in the ICU of the Beijing Ditan Hospital Capital Medical University. From June 1, 2005 to May 31, 2017, 225 cases were enrolled in this clinical study.

Results

122 (54.2%) patients were diagnosed with AKI during their stay in ICU, the number and percentage of AKI stage 1, 2 and 3 were 38 (31.1%), 21(17.2%) and 63(51.7%), respectively. 26.2% of AKI patients received CRRT during the stay of ICU. 56.25% CRRT patients died in ICU. The 28-day mortality was 62.5%, and the 90-day mortality was 75%. By univariate logistics analysis, it showed that higher likelihood of diagnosis for respiratory failure (OR = 7.333,95% CI 1.467–36.664,p = 0.015), higher likelihood of diagnosis for septic shock (OR = 1.005,95% CI 1.001–1.01,p = 0.018), and higher likelihood to use vasoactive agents (OR = 10.667,95% CI 1.743–65.271,p = 0.001), longer mechanical ventilation duration (OR = 1.011,95% CI 1.002–1.019,p = 0.011), higher likelihood for diagnosis for PCP (OR = 7.50,95% CI 1.288–43.687,p = 0.025), higher SOFA score at ICU admission (OR = 1.183,95% CI 1.012–1.383,p = 0.035), longer duration of CRRT (OR = 1.014,95% CI 1.001–1.028,p = 0.034) contributed to a higher mortality at ICU. The Cox Analysis for the cumulative survival of AKI 3 patients between the CRRT and non-CRRT groups shows no significant differences (p = 0.595).

Conclusions

There is a high incidence of AKI in HIV-infected patients admitted in our ICU. Patients with severe AKI were more prone to be admitted for CRRT and have a consequent poor prognosis.
Factors associated with 30-day and 1-year readmission among psychiatric inpatients in Beijing China: a retrospective, medical record-based analysis
Authors: Han Xueyan , Jiang Feng , Tang Yilang , Needleman Jack , Guo Moning , Chen Yin , Zhou Huixuan , Liu Yuanli
Published: March 2020

Background

Psychiatric readmissions negatively impact patients and their families while increasing healthcare costs. This study aimed at investigating factors associated with psychiatric readmissions within 30 days and 1 year of the index admissions and exploring the possibilities of monitoring and improving psychiatric care quality in China.

Methods

Data on index admission, subsequent admission(s), clinical and hospital-related factors were extracted in the inpatient medical record database covering 10 secondary and tertiary psychiatric hospitals in Beijing, China. Logistic regressions were used to examine the associations between 30-day and 1-year readmissions plus frequent readmissions (≥3 times/year), and clinical variables as well as hospital characteristics.

Results

The 30-day and 1-year psychiatric readmission rates were 16.69% (1289/7724) and 33.79% (2492/7374) respectively. 746/2492 patients (29.34%) were readmitted 3 times or more within a year (frequent readmissions). Factors significantly associated with the risk of both 30-day and 1-year readmission were residing in an urban area, having medical comorbidities, previous psychiatric admission(s), length of stay > 60 days in the index admission and being treated in tertiary hospitals (p < 0.001). Male patients were more likely to have frequent readmissions (OR 1.30, 95%CI 1.04–1.64). Receiving electroconvulsive therapy (ECT) was significantly associated with a lower risk of 30-day readmission (OR 0.72, 95%CI 0.56–0.91) and frequent readmissions (OR 0.60, 95%CI 0.40–0.91).

Conclusion

More than 30% of the psychiatric inpatients were readmitted within 1 year. Urban residents, those with medical comorbidities and previous psychiatric admission(s) or a longer length of stay were more likely to be readmitted, and men are more likely to be frequently readmitted. ECT treatment may reduce the likelihood of 30-day readmission and frequent admissions. Targeted interventions should be designed and piloted to effectively monitor and reduce psychiatric readmissions.
Social networks and quality of life among female breast cancer patients at Tikur Anbessa specialized hospital, Addis Ababa, Ethiopia 2019
Authors: Aberaraw Rahel , Boka Abdisa , Teshome Roza , Yeshambel Addisu
Published: March 2020

Background

Breast cancer is a major life-threatening global public health problem. It is the most common form of cancer in females in many developing countries including Ethiopia. Social networks could change the course of cancer and can influence the quality of life among breast cancer patients. Therefore, the purpose of this study was to assess social networks and quality of life among female breast cancer patients attending in Tikur Anbassa Specialized Hospital, Addis Ababa, Ethiopia 2019.

Methods

An institutional-based cross-sectional study was conducted in Tikur Anbessa Specialized Hospital Addis Ababa, Ethiopia from March 1 to April 30/2019. A total of 214 female breast cancer patients were included Binary and multiple logistic regression was used to show the association of social networks and quality of life.

Result

A total of 214 females with breast cancer were recruited with a mean age of 41.85. Participants who had children (AOR = 5, 95%CL: 1.3,21 COR = 6), and other relatives (AOR = 6, 95%CI: 1.2,30, COR = 7), were more likely to have good social networks. Participants who were not married (AOR = 0.02, 95%CI: 0.03, 0.28), had no parents living (AOR = 0.1, 95%CI: 0.02, 0.4), no close friends (AOR = 0.06, 95%CI: 0.01, 0.4), and no neighbors (AOR = 0.09, 95%CI: 0.03, 0.5) had poor social networks.

Conclusion

The quality of life was relatively low and social support were found to be poor in women with breast cancer. Health-care providers in oncology departments need to focus on addressing the side effects of therapy and social networks which may help to improve the quality of life of females with breast cancer.
The effect of counseling with a skills training approach on maternal functioning: a randomized controlled clinical trial
Authors: Chamgurdani Fatemeh Karami , Barkin Jennifer L. , Esmaeilpour Khalil , Malakouti Jamileh , Buoli Massimiliano , Mirghafourvand Mojgan
Published: March 2020

Background

The role of the mother can be deeply satisfying, but it is associated with many challenges including challenges during the postpartum period that may impede the optimal development of the infant. Therefore, the aim of the present study was to investigate the effects of counseling using the Skills Training Approach (STA) on postpartum maternal functioning.

Methods

This randomized controlled trial was performed on 68 postpartum women who referred to health centers of Tabriz-Iran in 2019. Participants were assigned to one of two groups - either counseling or control through the block randomization method. The intervention group received four counseling sessions using the Skills Training Approach (STA). Before and two weeks after the completion of the intervention, the Barkin Index of Maternal Functionning (BIMF) was completed by the participants. The independent t-test and ANCOVA (Analysis of Covariance) was used to analyze the data.

Results

There was no statistically significant difference between the two groups in terms of sociodemographic characteristics and the baseline scores of the BIMF and its domains (p > 0.05). Before the intervention, the mean (SD) total score of the BIMF in the intervention group was 73.1 (8.5) and in the control group, it was 71.6 (4.8). Post-intervention, the mean (SD) of the total score of the BIMF in the intervention group was 95.8 (11.8) and in the control group, it was 70.3 (4.5). Based on the ANCOVA test and after adjusting the baseline score, the mean total score of the BIMF was significantly higher in the intervention group than in the control group (Mean Difference (MD): 22.9; 95% CI: 18.2 to 27.6;p < 0.001). The post-intervention scores of all domains of the BIMF including self-care (MD: 3.8), infant care (MD: 2.0), mother-child interaction (MD: 4.8), psychological wellbeing (MD: 8.4), social support (MD: 4.0), management (MD: 6.8), and adjustment to new motherhood (MD: 3.2) were significantly higher in the intervention group compared to the control group (P < 0.001).

Conclusion

In this study, counseling, using STA, was effective in improving maternal functioning in all of the domains. This intervention, aimed at skill-building, should be strongly considered where improved postpartum functioning is the goal.

Trial registration

IRCT20120718010324N49. Registered 18 January 2019.