bluuebunny/crossref_metadata_2025_split huggingface dataset:
JAK2S523L, a novel gain-of-function mutation in a critical autoregulatory residue in JAK2V617F− MPNs
Authors: Pastore Friederike , Krishnan Aishwarya , Hammarén Henrik M. , Silvennoinen Olli , Yan Benedict , Levine Ross L. 
Published: September 2020

Abstract
The SH2-JH2 linker domain of JAK2 has been implicated in the negative regulation of JAK2 activity. In 2 patients with myeloproliferative neoplasms (MPNs), we identified and characterized the novel JAK2 mutation S523L, which occurs in a key residue in the linker region. In 1 case, acquisition of JAK2S523L was associated with thrombocytosis and bone marrow megakaryocytic hyperplasia, and there were no other somatic alterations in this patient. The second patient with JAK2S523Lmutation presented with increased hematocrit and had concurrent mutations in RUNX1 and BCORL1. Consistent with the genetic and clinical data, expression of JAK2S523L causes interleukin-3–independent growth in Ba/F3 cells transduced with the erythropoietin receptor by constitutively active Jak2/Stat5 signaling.
National clinical audit for hospitalised exacerbations of COPD
Authors: Hurst John R. , Quint Jennifer K. , Stone Robert A. , Silove Yvonne , Youde Jane , Roberts C. Michael 
Published: September 2020

IntroductionExacerbations of COPD requiring hospital admission are burdensome to patients and health services. Audit enables benchmarking performance between units and against national standards, and supports quality improvement. We summarise 23 years of UK audit for hospitalised COPD exacerbations to better understand which features of audit design have had most impact.MethodPilot audits were performed in 1997 and 2001, with national cross-sectional audits in 2003, 2008 and 2014. Continuous audit commenced in 2017. Overall, 96% of eligible units took part in cross-sectional audit, 86% in the most recent round of continuous audit. We synthesised data from eight rounds of national COPD audit.ResultsClinical outcomes were observed to change at the same time as changes in delivery of care: length of stay halved from 8 to 4 days between 1997 and 2014, alongside wider availability of integrated care. Process indicators did not generally improve with sequential cross-sectional audit. Under continuous audit with quality improvement support, process indicators linked to financial incentives (early specialist review (55–66%) and provision of a discharge bundle (53–74%)) improved more rapidly than those not linked (availability of spirometry (40–46%) and timely noninvasive ventilation (21–24%)).ConclusionCareful piloting and engagement can result in successful roll-out of cross-sectional national audit in a high-burden disease. Audit outcome measures and process indicators may be affected by changes in care pathways. Sequential cross-sectional national audit alone was not generally accompanied by improvements in care. However, improvements in process indicators were seen when continuous audit was combined with quality improvement support and, in particular, financial incentives.
Physical activity for cystic fibrosis: perceptions of people with cystic fibrosis, parents and healthcare professionals
Authors: Denford Sarah , Cox Narelle S. , Mackintosh Kelly A. , McNarry Melitta A. , O'Halloran Paul , Holland Anne E. , Tomlinson Owen W. , Barker Alan R. , Williams Craig A. 
Published: September 2020

BackgroundThe benefits of physical activity (PA) for people with cystic fibrosis (pwCF) are widely accepted, yet how PA is promoted and utilised by pwCF is unclear.MethodAn online questionnaire to explore attitudes, practices and promotion of PA in cystic fibrosis was completed by healthcare providers (HCP), pwCF and parents/caregivers.Results351 respondents (105 HCP, 120 pwCF, and 126 parents/caregivers) from 12 countries completed the survey. Importance of PA was rated highly by the majority of respondents. Physical (e.g.health), psychological (e.g.enjoyment) and social (e.g.social interaction) factors were motives for PA for 82%, 49% and 37% of pwCF, respectively, irrespective of country. Common barriers to PA included time (49% and 36%) and tiredness (61% and 7%) for pwCF and parents/carers, respectively. pwCF also reported psychosocial barriers (e.g.stigma, demoralisation), while parents/caregivers reported structural barriers (e.g.cost). Clinical teams varied substantially in terms of the emphasis placed on PA, facilities available, staff and training, and advice given to pwCF.ConclusionDespite the majority of participants rating the importance of PA highly, substantial variability was evident regarding the facilities and clinical support available to them, as well as why and how people were active. There remains a need to identify what constitutes “best practice” for PA promotion within clinics.
SHP2 inhibitor PHPS1 ameliorates acute kidney injury by Erk1/2-STAT3 signaling in a combined murine hemorrhage followed by septic challenge model
Authors: Jiang Jihong , Hu Baoji , Chung Chun-Shiang , Chen Yaping , Zhang Yunhe , Tindal Elizabeth W. , Li Jinbao , Ayala Alfred 
Published: September 2020

AbstractBackgroundHypovolemic shock and septic challenge are two major causes of acute kidney injury (AKI) in the clinic setting. Src homology 2 domain-containing phosphatase 2 (SHP2) is one of the major protein phosphatase tyrosine phosphatase (PTPs), which play a significant role in maintaining immunological homeostasis by regulating many facets of immune cell signaling. In this study, we explored whether SHP2 signaling contributed to development of AKI sequential hemorrhage (Hem) and cecal ligation and puncture (CLP) and whether inactivation of SHP2 through administration of its selective inhibitor, phenylhydrazonopyrazolone sulfonate 1 (PHPS1), attenuated this injury.MethodsMale C57BL/6 mice were subjected to Hem (a “priming” insult) followed by CLP or sham-Hem plus sham-CLP (S/S) as controls. Samples of blood and kidney were harvested at 24 h post CLP. The expression of neutrophil gelatinase-associated lipocalin (NGAL), high mobility group box 1 (HMGB1), caspase3 as well as SHP2:phospho-SHP2, extracellular-regulated kinase (Erk1/2): phospho-Erk1/2, and signal transducer and activator of transcription 3 (STAT3):phospho-STAT3 protein in kidney tissues were detected by Western blotting. The levels of creatinine (Cre) and blood urea nitrogen (BUN) in serum were measured according to the manufacturer’s instructions. Blood inflammatory cytokine/chemokine levels were detected by ELISA.ResultsWe found that indices of kidney injury, including levels of BUN, Cre and NGAL as well as histopathologic changes, were significantly increased after Hem/CLP in comparison with that in the S/S group. Furthermore, Hem/CLP resulted in elevated serum levels of inflammatory cytokines/chemokines, and induced increased levels of HMGB1, SHP2:phospho-SHP2, Erk1/2:phospho-Erk1/2, and STAT3:phospho-STAT3 protein expression in the kidney. Treatment with PHPS1 markedly attenuated these Hem/CLP-induced changes.ConclusionsIn conclusion, our data indicate that SHP2 inhibition attenuates AKI induced by our double-hit/sequential insult model of Hem/CLP and that this protective action may be attributable to its ability to mitigate activation of the Erk1/2 and STAT3 signaling pathway. We believe this is a potentially important finding with clinical implications warranting further investigation.
Effects of residual lignin and cellulose swelling on the rate of enzymatic saccharification of softwood and hardwood acid sulfite pulps
Authors: Tanifuji Keishi , Nakagawa-izumi Akiko , Ohi Hiroshi 
Published: September 2020

AbstractWe estimated the effect of residual lignin and pulp swelling on the rate of enzymatic saccharification to increase production of ethanol from acid sulfite pulp (SP) by means of enzymatic treatment. The resolution ratio of hardwood (Acacia mearnsii) SP after the enzymatic treatment was lower compared to softwood (Larix leptolepis) SP even though lignin content of hardwood SP was lower. The pyrolysis–gas chromatography/mass spectrometry (Py-GC/MS) analysis revealed that the residual lignin in hardwood SP could more easily adsorb enzyme compared to softwood SP, and the residual lignin in hardwood SP should interfere with the binding of the enzyme to cellulose. The beating treatment of pulp increased the swelling of pulp. The enzymatic saccharification rate was increased by the beating treatment. On the other hand, the delignification treatment was more effective than the beating treatment at enhancing enzymatic saccharification of both hardwood and softwood SPs. We found that the delignification process should be considered a high-priority technique for enhancing enzymatic saccharification of SP.
Building stock market resilience through digital transformation: using Google trends to analyze the impact of COVID-19 pandemic
Authors: Ding Ding , Guan Chong , Chan Calvin M. L. , Liu Wenting 
Published: September 2020

AbstractAs the 2019 novel coronavirus disease (COVID-19) pandemic rages globally, its impact has been felt in the stock markets around the world. Amidst the gloomy economic outlook, certain sectors seem to have survived better than others. This paper aims to investigate the sectors that have performed better even as market sentiment is affected by the pandemic. The daily closing stock prices of a total usable sample of 1,567 firms from 37 sectors are first analyzed using a combination of hierarchical clustering and shape-based distance (SBD) measures. Market sentiment is modeled from Google Trends on the COVID-19 pandemic. This is then analyzed against the time series of daily closing stock prices using augmented vector autoregression (VAR). The empirical results indicate that market sentiment towards the pandemic has significant effects on the stock prices of the sectors. Particularly, the stock price performance across sectors is differentiated by the level of the digital transformation of sectors, with those that are most digitally transformed, showing resilience towards negative market sentiment on the pandemic. This study contributes to the existing literature by incorporating search trends to analyze market sentiment, and by showing that digital transformation moderated the stock market resilience of firms against concern over the COVID-19 outbreak.
Identification of single nucleotide variants in the Moroccan population by whole-genome sequencing
Authors: Crooks Lucy , Cooper-Knock Johnathan , Heath Paul R. , Bouhouche Ahmed , Elfahime Mostafa , Azzouz Mimoun , Bakri Youssef , Adnaoui Mohammed , Ibrahimi Azeddine , Amzazi Saaïd , Tazi-Ahnini Rachid 
Published: September 2020

Abstract
Background
Large-scale human sequencing projects have described around a hundred-million single nucleotide variants (SNVs). These studies have predominately involved individuals with European ancestry despite the fact that genetic diversity is expected to be highest in Africa where Homo sapiens evolved and has maintained a large population for the longest time. The African Genome Variation Project examined several African populations but these were all located south of the Sahara. Morocco is on the northwest coast of Africa and mostly lies north of the Sahara, which makes it very attractive for studying genetic diversity. The ancestry of present-day Moroccans is unknown and may be substantially different from Africans found South of the Sahara desert, Recent genomic data of Taforalt individuals in Eastern Morocco revealed 15,000-year-old modern humans and suggested that North African individuals may be genetically distinct from previously studied African populations.

Results
We present SNVs discovered by whole genome sequencing (WGS) of three Moroccans. From a total of 5.9 million SNVs detected, over 200,000 were not identified by 1000G and were not in the extensive gnomAD database. We summarise the SNVs by genomic position, type of sequence gene context and effect on proteins encoded by the sequence. Analysis of the overall genomic information of the Moroccan individuals to individuals from 1000G supports the Moroccan population being distinct from both sub-Saharan African and European populations.

Conclusions
We conclude that Moroccan samples are genetically distinct and lie in the middle of the previously observed cline between populations of European and African ancestry. WGS of Moroccan individuals can identify a large number of novel SNVs and aid in functional characterisation of the genome.
Type IV choledochal cyst with polycystic kidney disease: a case report
Authors: He Yuxin , Yu Zhuwen , Chen Weichang 
Published: September 2020

Abstract
Background
Choledochal cysts are divided into 5 types. Physicians believe that Caroli disease (which refers to type V biliary cysts) is a special type of biliary cyst caused by a mutation in the PKHD1 gene and is associated with autosomal recessive polycystic kidney disease (ARPKD). There is currently no clear association between other types of choledochal cysts and polycystic kidney disease.

Case presentation
We report a 65-year-old male patient with jaundice, decreased appetite, and itchy skin. His biochemistry test results indicated obstructive jaundice disease. Cross-sectional imaging showed a type IVA choledochal cyst accompanied by autosomal dominant polycystic kidney disease (ADPKD). Due to economic difficulties, the patient achieved percutaneous transhepatic cholangial drainage (PTCD) instead of surgery.

Conclusion
To our knowledge, this is the second case report of the coexistence of type IVA choledochal cysts and ADPKD. We conclude that it is vital to be aware that the above condition is a possibility. This case report will aid earlier diagnosis and management and possibly prevent further damage to liver and kidney function.
Association of sleep duration with risk of all-cause mortality and poor quality of dying in oldest-old people: a community-based longitudinal study
Authors: Hou Chengbei , Lin Yinan , Zimmer Zachary , Tse Lap Ah. , Fang Xianghua 
Published: September 2020

Abstract
Background
While sleep duration has been shown to be associated with health outcomes, few studies have been conducted among the oldest old. In addition, the impact of sleep duration on quality of dying is unknown. We aimed to evaluate how sleep duration affects all-cause mortality and quality of dying in people aged 80 + .

Methods
This community-based longitudinal study was performed by using data from 15,048 individuals aged ≥80 with information on sleep duration in the Chinese Longitudinal Healthy Longevity Survey. Cox and logistic regression models with penalized splines were applied to explore the shape of the association between sleep duration and all-cause mortality and poor quality of dying respectively and identify the interval of sleep duration resulting in the lowest risk of both.

Results
During a median follow-up of 3.1 years, 11,582 deaths including 4116 individuals who experienced poor quality of dying were recorded. Sleep duration showed a U-shaped association with all-cause mortality and sleeping about 8 h had the minimum risk of death; a J-shaped association was found between sleep duration and poor quality of dying. Compared with sleep duration of 7–9 h, the adjusted hazard ratio of total deaths was 1.08 (95% CI 1.03–1.13) for short duration (< 7 h) and 1.12 (95% CI 1.07–1.17) for long duration (> 9 h); the adjusted odds ratio of poor QOD was 1.10 (95% CI 1.01–1.21) for long duration, but this association was restricted to those with baseline unhealthy status (P-interaction = 0.04).

Conclusions
Sleeping a little longer may be better for individuals over 80 years old, and sleep duration of 7–9 h per day is optimal for both survival and good quality of life near death.
Proteinuria as a presenting sign of combined methylmalonic acidemia and homocysteinemia: case report
Authors: Chen Ru-Yue , Li Xiao-Zhong , Lin Qiang , Zhu Yun , Shen Yun-Yan , Xu Qin-Ying , Zhu Xue-Ming , Chen Lin-Qi , Wu Hai-Ying , Chen Xu-Qin 
Published: September 2020

Abstract
Background
Disorders of the metabolism and absorption of vitamin B12 can lead to decrease in activity of methionine synthetase and methylmalonate coenzyme A mutase (MMUT), which results in increased levels of methylmalonic acid and homocysteine in blood and urine. Often, combined methylmalonic acidemia (MMA) and homocysteinemia is misdiagnosed due to a lack of specific symptoms. The clinical manifestations are diverse, but proteinuria as the initial presentation is rare.

Case presentation
Two cases of MMA with homocysteinemia in children are reported. Proteinuria were a primary presenting symptom, followed by anemia and neurologic symptoms (frequent convulsions and unstable walking, respectively). Screening of amino acids and acyl carnitine in serum showed that the propionyl carnitine:acetylcarnitine ratio increased. Profiling of urinary organic acids by gas chromatography–mass spectrometry revealed high levels of methylmalonic acid. Homocysteine content in blood was increased. Comprehensive genetic analyses of peripheral blood-derived DNA demonstrated heterozygous variants of methylmalonic aciduria type C and homocystinuria (MMACHC) and amnionless (AMN) genes in our two patients, respectively. After active treatment, the clinical manifestations in Case 1 were relieved and urinary protein ceased to be observed; Case 2 had persistent proteinuria and was lost to follow-up.

Conclusions
Analyses of the organic acids in blood and urine suggested MMA combined with homocysteinemia. In such diseases, reports of renal damage are uncommon and proteinuria as the initial presentation is rare. Molecular analysis indicated two different genetic causes. Although the pathologic mechanisms were related to vitamin B12, the severity and prognosis of renal lesions were different. Therefore, gene detection provides new insights into inherited metabolic diseases.
Grow well/Crecer bien: a protocol for research on infant feeding practices in low-income families
Authors: Cheney Ann M. , Nieri Tanya , Ramirez Zarate Ana , Garcia Gretel , Vaca Lucero , Valencia Esmirna , Versteeg Colleen , Molina Arlene , Castillo Michael , Tovar Alison 
Published: September 2020

Abstract
Background
The prevalence of obesity among children remains high. Given obesity’s significant lifelong consequences, there is great interest in preventing obesity early in life. There is a need to better understand the relation of common infant feeding styles and practices to obesity in infants using longitudinal study designs. There is also an urgent need to understand the role of caregivers other than mothers in feeding. A better understanding of variation in feeding styles and practices can inform the identification of risk groups and the tailoring of interventions to them.

Methods
In partnership with Early Head Start programs across four counties in southern California, mothers and infants will be enrolled in a two-year longitudinal study collecting survey and anthropometric data. A subsample of mothers and their selected other caregivers will participate in qualitative research involving feeding diaries and dyadic interviews. The results will be used to develop and test an enhanced nutrition education program.

Discussion
We outline a study methodology to examine feeding styles and practices and their association with early childhood obesity risk and enhance an existing intervention to promote healthy infant feeding and growth among children in low-income families.
Spatial distribution of tuberculosis incidence in Los Angeles County
Authors: Readhead Adam , Chang Alicia H. , Ghosh Jo Kay , Sorvillo Frank , Higashi Julie , Detels Roger 
Published: September 2020

Abstract
Background
In Los Angeles County, the tuberculosis (TB) disease incidence rate is seven times higher among non-U.S.-born persons than U.S.-born persons and varies by country of birth. But translating these findings into public health action requires more granular information, especially considering that Los Angeles County is more than 4000 mile2. Local public health authorities may benefit from data on which areas of the county are most affected, yet these data remain largely unreported in part because of limitations of sparse data. We aimed to describe the spatial distribution of TB disease incidence in Los Angeles County while addressing challenges arising from sparse data and accounting for known cofactors.

Methods
Data on 5447 TB cases from Los Angeles County were combined with stratified population estimates available from the 2005–2011 Public Use Microdata Survey. TB disease incidence rates stratified by country of birth and Public Use Microdata Area were calculated and spatial smoothing was applied using a conditional autoregressive model. We used Bayesian Poisson models to investigate spatial patterns adjusting for age, sex, country of birth and years since initial arrival in the U.S.

Results
There were notable differences in the crude and spatially-smoothed maps of TB disease rates for high-risk subgroups, namely persons born in Mexico, Vietnam or the Philippines. Spatially-smoothed maps showed areas of high incidence in downtown Los Angeles and surrounding areas for persons born in the Philippines or Vietnam. Areas of high incidence were more dispersed for persons born in Mexico. Adjusted models suggested that the spatial distribution of TB disease could not be fully explained using age, sex, country of birth and years since initial arrival.

Conclusions
This study highlights areas of high TB incidence within Los Angeles County both for U.S.-born cases and for cases born in Mexico, Vietnam or the Philippines. It also highlights areas that had high incidence rates even when accounting for non-spatial error and country of birth, age, sex, and years since initial arrival in the U.S. Information on spatial distribution provided here complements other descriptions of local disease burden and may help focus ongoing efforts to scale up testing for TB infection and treatment among high-risk subgroups.
Effect of chlorhexidine chip as an adjunct in non-surgical management of periodontal pockets: a meta-analysis
Authors: Ma Lili , Diao Xiuchun 
Published: September 2020

Abstract
Background
The aim of this meta-analysis was to evaluate the difference in treatment outcomes between sub-gingival placement of chlorhexidine chip (CHX chip) in adjunct to scaling and root planing (SRP) and SRP alone for the management of periodontal pockets in patients suffering from chronic periodontitis.

Methods
We searched the MEDLINE (PubMed), SCOPUS and CENTRAL databases and identified 15 randomized clinical trials published within the last decade (2007–2019): 9 with split-mouth design and 6 with parallel study design. We extracted data and performed both qualitative and quantitative syntheses. The primary outcomes assessed were gain in clinical attachment level (CAL), reduction in probing pocket depth (PPD), improvement in gingival inflammation, and results of microbiological assays.

Results
We used meta-analysis plots to assess all the clinical outcomes. The mean differences in PPD reductions at 1 month (MD 0.63), 3 months (MD 0.69), and 6 months (MD 0.75); and the CAL gains at 1 month (MD 0.54), 3 months (MD 0.64), and 6 months (MD 0.68) showed more favorable responses in sites treated with the CHX chip as an adjuvant to SRP, than in sites treated with SRP alone.

Conclusion
SRP with adjunctive CHX chips showed better clinical outcomes than SRP alone for the management of periodontal pockets in patients with chronic periodontitis.