bluuebunny/crossref_metadata_2025_split huggingface dataset:
Late-onset severe hepatic sinusoidal obstruction syndrome in an allogeneic stem cell transplant recipient
Authors: Sun Yan-ling , Liu Ling-ling , He Yi , Zhang Jing-wen , Wen Rui-juan , Yuan Qing , Wang Xin , Guo Ruo-mi , Li Xu-dong , Long Bing 
Published: October 2020

Abstract

Rationale:
Hepatic sinusoidal obstruction syndrome (SOS) is a rare and potentially fatal complications after hematopoietic stem cell transplantation (HSCT). Most severe SOS result in multi-organ dysfunction and are associated with a high mortality rate (>80%).

Patient concerns:
A 31-year-old man was diagnosed with chronic myeloid leukemia blast crisis. He presented with severe thrombocytopenia on day 42 post-HSCT (on days +42), gradually developed with painful hepatomegaly, ascites, and weight gain.

Diagnoses:
The abdominal computerized tomography showed hepatomegaly, hepatic congestion, periportal edema, narrow hepatic vein, and ascites suggestive of SOS/hepatic vein occlusion. According to the EBMT revised diagnostic criteria, the patient was diagnosed as late-onset severe SOS.

Interventions:
Comprehensive treatment including low molecular weight heparin was initiated.

Outcomes:
The patient had good response with resolution of his hepatomegaly, increase of platelet, weight and transaminase loss after 4 weeks treatment.

Lessons:
In SOS patients with nonspecific clinical and biochemical findings, computerized tomography scans can be useful in differentiating SOS from other complications after HSCT. low molecular weight heparin is effective for the treatment of SOS.
The combination of excimer laser ablation and drug eluting balloon for treating superficial femoral arterial occlusion following stent implantation
Authors: Wu Xueliang , Wang Zhao , Li Tian 
Published: October 2020

Abstract

Rationale:
Recent research shows that in-stent restenosis (ISR) occurs in half of the patients treated with stenting of femoral and popliteal artery for lower extremity arteriosclerotic occlusive disease (LEASO). Combined therapy is mainly used clinically to obtain better medium- and long-term treatment outcomes and reduce the occurrences of reintervention, among which, the combination of excimer laser ablation (ELA) and drug eluting balloon (DEB) is a new and effective choice.

Patient concerns:
A 76-year-old male patient with ISR of right superficial femoral artery after stent implantation was reported.

Diagnosis:
Rechecking angiography indicated severe occlusion of the right superficial femoral artery. The physical examination showed that bilateral femoral and popliteal arteries were accessible whereas right dorsalis and posterior tibial arteries are unaccessible. Ankleolus brachial index (ABI) was 0.92 for left and 0.58 for right.

Interventions:
We performed the operation with ELA and drug balloon DEB on the right superficial femoral artery under local anesthesia and treated with oral antiplatelet drugs after operation.

Outcomes:
The combination treatment was very successful, and postoperative lower extremity arteriogram showed the blood flow was fluent and fast. No recurrence was discovered 3 months after the operation and he had no obvious symptom of claudication.

Lessons:
The combination of ELA and DEB is useful and effective for ISR of peripheral vessel after stent implantation, and this surgical method is worthwhile but need further clinical research for safety confirmation.
Eight rare urinary disorders in a patient with Kallmann syndrome
Authors: Tian Huining , Yan Zi , Lv You , Sun Lin , Gang Xiaokun , Wang Guixia 
Published: October 2020

Abstract

Rationale:
Kallmann syndrome (KS) is a rare inherited genetic disorder characterized by hypogonadotropic hypogonadism and hyposmia/anosmia. Early diagnosis is the key to timely treatment and improvement of prognosis in patients with KS. As the most common complication of KS, renal agenesis can provide clues to early diagnosis and treatment for KS. In this article, we report a case of KS with 8 rare urinary disorders for the first time.

Patient concerns:
A 19-year-old Chinese man presented with 8 rare urinary disorders and a history of bilateral cryptorchidism came to us for micropenis, hyposmia, and delayed puberty.

Diagnosis:
The patient presented with hyposmia, low levels of sex hormones and showed a weak response to the GnRH stimulation test leading to a diagnosis of KS. Two missense mutations were found in further whole-exome sequencing: 1) Kallmann syndrome 1 (KAL1) gene in exon11, c.1600G > A, p. Val534Ile; 2) Prokineticin receptor 2 (PROKR2) gene in exon 2, c.533G > A, p. Trp178Ser. which led to a diagnosis of KS.

Interventions:
The patient underwent replacement therapy of human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG). The patient had previously undergone six surgeries for cryptorchidism and urinary disorders.

Outcomes:
The patient's puberty retardation was effectively alleviated. His serum testosterone (T) reached a normal level (8.280 nmol/mL). During the follow-up period, he presented with Tanner stage II pubic hair development.

Conclusion:
In this article, we report 8 rare urinary disorders with missense mutations of KAL1 and PROKR2 in a case of KS. Among them, bilateral giant kidneys, urinary extravasation of right renal, bilateral megalo-ureters, left ureteral terminal obstruction, bilateral renal cyst and bladder emptying disorder are reported for the first time, which enrich the integrity of urinary disorder types and provide clues to genetic counseling in patients with KS.
Central diabetes insipidus unveiled by glucocorticoid therapy in a patient with an empty sella
Authors: Yang Lei-Yi , Lin Sang , Xie Qi-Bing , Yin Geng 
Published: October 2020

Abstract

Rationale:
Some diseases contribute to hypopituitarism without clinical manifestations and the glucocorticoid therapy may unveil central diabetes insipidus. The condition is rare and usually causes problems for clinical physicians.

Patient concerns:
A 59-year-old woman presented to our hospital due to facial numbness and persistent eyelid heaviness.

Diagnosis:
Physical examination and cerebrospinal fluid examination supported a diagnosis of Guillain–Barré syndrome. Magnetic resonance imaging showed an empty sella. Hormone test indicated hypopituitarism.

Interventions:
The patient received intravenous immunoglobulin and glucocorticoid. Central diabetes insipidus appeared after 20 days. Subsequently, the patient was prescribed 1-desamino-8-D-arginine vasopressin and prednisone.

Outcomes:
During 6 months’ follow-up, the patient's urine output was gradually reduced to normal level.

Lessons:
This case indicated that hypopituitarism may be caused by an empty sella and be masked by adrenal insufficiency. Central diabetes insipidus may present after glucocorticoid therapy.
Acute encephalopathy with biphasic seizures and late reduced diffusion
Authors: Ma Yan-li , Xu Kai-li , Chen Guo-hong , Wang Li , Wang Yuan , Jin Zhi-peng 
Published: October 2020

Abstract

Rationale:
Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) has been reported almost exclusively in the Japanese population.

Patient concerns:
A 17-month-old male patient presented with fever and seizures, and subsequently fell into a coma. On the second day, he recovered consciousness. On the fourth day, he developed complex partial seizures and fell into a coma again. On day 10, the fever and seizures subsided. Head computed tomography on the first day showed no abnormalities. Brain diffusion-weighted images on the fourth day revealed reduced diffusion in the bilateral subcortical white matter.

Diagnosis:
A diagnosis of AESD was made.

Interventions:
The patient was treated with corticosteroids and intravenous immunoglobulin.

Outcomes:
At the 4-month follow-up, the patient was able to walk independently, and the epileptic seizures were well controlled.

Lessons:
AESD is a rare entity, and treatment with corticosteroids and intravenous immunoglobulin can lead to a favorable prognosis. Clinicians should be aware of this condition, and clinicoradiological features can suggest the diagnosis.
Clinical impact of echocardiography-defined pulmonary hypertension on the clinical outcome in patients with multiple myeloma
Authors: Bae SungA , Kim Kye Hun , Yoon Hyun Ju , Kim Hyung Yoon , Park Hyukjin , Cho Jae Yeong , Kim Min Chul , Kim Yongcheol , Hong Young Joon , Park Hyung Wook , Kim Ju Han , Ahn Youngkeun , Jeong Myung Ho , Cho Jeong Gwan , Park Jong Chun 
Published: October 2020

Abstract
Pulmonary hypertension (PH) is a complication of multiple myeloma (MM); however, the clinical outcomes and prognosis are relatively not well known. We aimed to investigate the risk factors of transthoracic echocardiography-defined PH and its impact on the clinical outcome in patients with MM.
A retrospective study was performed using data from the Chonnam National University Hwasun Hospital database for patients who underwent transthoracic echocardiography (TTE) within 1 month of the MM diagnosis between January 2007 and December 2017. PH was defined as an estimated right ventricular systolic pressure (RVSP) > 40 mmHg. A total of 390 patients were included. TTE-defined PH was observed in 107 patients (27%). During the follow-up period (median, 688 days), all-cause death was noted for 134 patients (34.4%). In the Kaplan-Meier survival analysis, the cumulative overall survival and cardiovascular death-free survival rates were significantly lower in the PH group than in the non-PH group (P < .001). In the propensity score-matched population, RVSP > 40 mmHg on TTE and history of congestive heart failure (CHF) were identified as the significant independent predictors of all-cause and cardiovascular death.
This study reports that the prevalence of TTE-defined PH is higher in patients with MM than in the general population. Moreover, TTE-defined PH and a history of CHF are the independent prognostic factors for all-cause and cardiovascular death in patients with MM. These results highlight the risk of associated cardiovascular disease in patients with MM and emphasize the importance of management strategies that prevent the deterioration of cardiac function.
Characterization of a COPD-Associated NPNT Functional Splicing Genetic Variant in Human Lung Tissue via Long-Read Sequencing
Authors: Saferali Aabida , Xu Zhonghui , Sheynkman Gloria M. , Hersh Craig P. , Cho Michael H. , Silverman Edwin K. , Laederach Alain , Vollmers Christopher , Castaldi Peter J. 
Published: October 2020

AbstractChronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. Genome-wide association studies (GWAS) have identified over 80 loci that are associated with COPD and emphysema, however for most of these loci the causal variant and gene are unknown. Here, we utilize lung splice quantitative trait loci (sQTL) data from the Genotype-Tissue Expression project (GTEx) and short read sequencing data from the Lung Tissue Research Consortium (LTRC) to characterize a locus in nephronectin (NPNT) associated with COPD case-control status and lung function. We found that the rs34712979 variant is associated with alternative splice junction use in NPNT, specifically for the junction connecting the 2nd and 4th exons (chr4:105898001-105927336) (p=4.02×10−38). This association colocalized with GWAS data for COPD and lung spirometry measures with a posterior probability of 94%, indicating that the same causal genetic variants in NPNT underlie the associations with COPD risk, spirometric measures of lung function, and splicing. Investigation of NPNT short read sequencing revealed that rs34712979 creates a cryptic splice acceptor site which results in the inclusion of a 3 nucleotide exon extension, coding for a serine residue near the N-terminus of the protein. Using Oxford Nanopore Technologies (ONT) long read sequencing we identified 13 NPNT isoforms, 6 of which are predicted to be protein coding. Two of these are full length isoforms which differ only in the 3 nucleotide exon extension whose occurrence differs by genotype. Overall, our data indicate that rs34712979 modulates COPD risk and lung function by creating a novel splice acceptor which results in the inclusion of a 3 nucelotide sequence coding for a serine in the nephronectin protein sequence. Our findings implicate NPNT splicing in contributing to COPD risk, and identify a novel serine insertion in the nephronectin protein that warrants further study.
Analytical evaluation and critical appraisal of early commercial SARS-CoV-2 immunoassays for routine use in a diagnostic laboratory
Authors: Cramer Amanda , Goodman Nigel , Cross Timothy , Gant Vanya , Dziadzio Magdalena 
Published: October 2020

AbstractBACKGROUNDThe objective of this study was to evaluate the performance characteristics of early commercial SARS-CoV-2 antibody assays in mild and asymptomatic subjects to enable the selection of suitable serological assays for routine diagnostic use within HCA Healthcare UK.METHODSWe used serum samples from a pre-Covid era patient cohort (n=50, pre-December 2019), designated SARS-CoV-2 negative, and serum samples from a SARS-CoV-2 RT-PCR-positive cohort (n=90) taken > 14 days post symptom onset (April-May 2020). We evaluated 6 ELISA assays including one confirmation assay to investigate antibody specificity. We also evaluated one point-of-care lateral flow device and one high throughput electrochemiluminescence immunoassay.RESULTSThe ELISA specificities ranged from 84-100%, with sensitivities ranging from 75.3-90.0%. The LFIA showed 100% specificity and 80% sensitivity using smaller sample numbers. The Roche CLIA immunoassay showed 100% specificity and 90.7% sensitivity. When used in conjunction, the Euroimmun nucleocapsid (NC) and spike-1 (S1) IgG ELISA assays had a sensitivity of 95.6%. The confirmation IgG assay showed 92.6% of samples tested contained both NC and S1 antibodies, 32.7% had NC, S1 and S2 and 0% had either S1 or S2 only.CONCLUSIONSThese first generation assays were not calibrated against reference material and the results are reported qualitatively. The Roche assay and the Euroimmun NC and S1 assays had the best sensitivity overall in our hands. Combining the assays detecting NC and S1/S2 antibody increased diagnostic yield. A portfolio of next generation SARS-CoV-2 immunoassays will be necessary in any future studies of herd and vaccine induced immunity.
The Abelson tyrosine kinase and the Nedd4-family ubiquitin ligase Suppressor of Deltex converge at the Notch PPxY motif to regulate endosomal trafficking and signaling
Authors: Sanchez-Luege Nicelio , Miranda-Alban Julio , Sun Xiao , Valbuena Fernando M. , Glick Benjamin S. , Rebay Ilaria 
Published: October 2020

AbstractThe conserved Notch signaling pathway coordinates diverse cellular processes during animal development. Unlike most cell surface receptors that use a cytoplasmic cascade to amplify and diversify signaling dynamics, Notch itself transduces external cues directly to the nucleus. How appropriate signaling dynamics and transcriptional responses are achieved with this pathway architecture remains unclear. Here, we report that the cytoplasmic tyrosine kinase Abelson (Abl) fine-tunes Notch signaling by regulating Notch endocytic trafficking. We show that Abl can directly phosphorylate a PPxY motif important for Nedd4-family ubiquitin-ligase-mediated transfer of Notch into degradative endosomal compartments. Consistent with this, loss of Abl or inhibition of its kinase activity results in aberrant endosomal accumulation of Notch, while mutation of the PPxY tyrosine renders Notch insensitive to such regulation. Phenotypic and genetic interaction studies in the wing, together with parallel assays in cultured cells, show that loss or gain of Abl activity can respectively increase or decrease Notch output. We propose that the Notch PPxY motif operates as a molecular hub that integrates multiple post-translational modifications to regulate Notch trafficking and fine-tune signaling output.
Health Complexity Assessment in Primary Care: a validity and feasibility study of the INTERMED tool
Authors: de Oliveira Camila Almeida , Weber Bernardete , dos Santos Jair Lício Ferreira , Zucoloto Miriane Lucindo , de Camargo Lisa Laredo , Zanetti Ana Carolina Guidorizzi , Rzewuska Magdalena , de Azevedo-Marques João Mazzoncini 
Published: October 2020

AbstractBackgroundWhile considerable attention has been devoted to patients’ health complexity epidemiology, comparatively less attention has been paid to tools to identify and describe, in a personalized and comprehensive way, “complex patients” in primary health care (PHC).ObjectiveTo evaluate INTERMED tool’s validity and feasibility to assess health complexity in PHC.DesignCross-sectional psychometric study.SettingThree Brazilian PHC Units.Participants230 patients above 18 years of both sexes.MeasurementsSpearman’s rho assessed concurrent validity between the whole INTERMED and their four domains (biological, psychological, social, health system) with other well-validated instruments. Pearson’s X2 measured associations of the sum of INTERMED “current state” items with use of PHC, other health services and medications. Cronbach’s Alpha assessed internal consistency. INTERMED acceptability was measured through patients’ views on questions and answers’ understanding and application length as well as objective application length. Applicability was measured through patients’ views on its relevance to describe health aspects essential to care and INTERMED’s items-related information already existing in patients’ health records.Results18.3% of the patients were “complex” (INTERMED’s 20/21 cut-off). Spearman’s correlations located between 0.44 - 0.65. Pearson’s coefficients found were X2 = 26.812 and X2 = 26.883 (both p = 0.020) and X2 = 28.270 (p = 0.013). Cronbach’s Alpha was 0.802. All patients’ views were very favorable. Median application time was 7 minutes and 90% of the INTERMED’s interviews took up to 14 minutes. Only the biological domain had all its items described in more than 50% of the health records.LimitationsWe utilized the cutoff point used in all previous studies, found in research performed in specialized health services.ConclusionWe found good feasibility (acceptability and applicability), and validity measures comparable to those found from specialized health services. Further investigations of INTERMED predictive validity and suitability for routine PHC use are worthwhile.
Simulation and prediction of spread of COVID-19 in The Republic of Serbia by SEIRDS model of disease transmission
Authors: Stanojevic Slavoljub , Ponjavic Mirza , Stanojevic Slobodan , Stevanovic Aleksandar , Radojicic Sonja 
Published: October 2020

AbstractAs a response to the pandemic caused by SARS-Cov-2 virus, on 15 March, 2020, the Republic of Serbia introduced comprehensive anti-epidemic measures to curb COVID-19. After a slowdown in the epidemic, on 6 May, 2020, the regulatory authorities decided to relax the implemented measures. However, the epidemiological situation soon worsened again. As of 7 February, 2021, a total of 406,352 cases of SARSCov-2 infection have been reported in Serbia, 4,112 deaths caused by COVID-19. In order to better understand the epidemic dynamics and predict possible outcomes, we have developed an adaptive mathematical model SEAIHRDS (S-susceptible, E-exposed, A-asymptomatic, I-infected, H-hospitalized, R-recovered, D-dead due to COVID-19 infection, S-susceptible). The model can be used to simulate various scenarios of the implemented intervention measures and calculate possible epidemic outcomes, including the necessary hospital capacities. Considering promising results regarding the development of a vaccine against COVID-19, the model is extended to simulate vaccination among different population strata. The findings from various simulation scenarios have shown that, with implementation of strict measures of contact reduction, it is possible to control COVID-19 and reduce number of deaths. The findings also show that limiting effective contacts within the most susceptible population strata merits a special attention. However, the findings also show that the disease has a potential to remain in the population for a long time, likely with a seasonal pattern. If a vaccine, with efficacy equal or higher than 65%, becomes available it could help to significantly slow down or completely stop circulation of the virus in human population.The effects of vaccination depend primarily on: 1. Efficacy of available vaccine(s), 2. Prioritization of the population categories for vaccination, and 3. Overall vaccination coverage of the population, assuming that the vaccine(s) develop solid immunity in vaccinated individuals. With expected basic reproduction number of Ro=2.46 and vaccine efficacy of 68%, an 87% coverage would be sufficient to stop the virus circulation.
Girding the loins? Direct evidence of the use of a medieval parchment birthing girdle from biomolecular analysis
Authors: Fiddyment Sarah , Goodison Natalie J. , Brenner Elma , Signorello Stefania , Price Kierri , Collins Matthew J. 
Published: October 2020

AbstractIn this paper we describe a dry non-invasive extraction method to detect palaeoproteomic evidence from stained manuscripts. The manuscript analysed in this study is a medieval parchment birth girdle (Wellcome Collection Western MS. 632) made in England and thought to be used by pregnant women while giving birth. Using a dry non-invasive sampling method we were able to extract both human and non-human peptides from the stains, including evidence for the use of honey, cereals, ovicaprine milk and legumes. In addition, a large number of human peptides were detected on the birth roll, many of which are found in cervico-vaginal fluid. This suggests that the birth roll was actively used during childbirth. This study is the first to extract and analyse non-collagenous peptides from a parchment document using a dry non-invasive sampling method and demonstrates the potential of this type of analysis for stained manuscripts, providing direct biomolecular evidence for active use.
Potential Achilles heels of SARS-CoV-2 are best displayed by the base order-dependent component of RNA folding energy
Authors: Zhang Chiyu , Forsdyke Donald R. 
Published: October 2020

ABSTRACTThe base order-dependent component of folding energy has revealed a highly conserved region in HIV-1 genomes that associates with RNA structure. This corresponds to a packaging signal that is recognized by the nucleocapsid domain of the Gag polyprotein. Long viewed as a potential HIV-1 “Achilles heel,” the signal can be targeted by a new antiviral compound. Although SARS-CoV-2 differs in many respects from HIV-1, the same technology displays regions with a high base order-dependent folding energy component, which are also highly conserved. This indicates structural invariance (SI) sustained by natural selection. While the regions are often also protein-encoding (e.g. NSP3, ORF3a), we suggest that their nucleic acid level functions can be considered potential “Achilles heels” for SARS-CoV-2, perhaps susceptible to therapies like those envisaged for AIDS. The ribosomal frameshifting element scored well, but higher SI scores were obtained in other regions, including those encoding NSP13 and the nucleocapsid (N) protein.