bluuebunny/crossref_metadata_2025_split huggingface dataset:
Community-led initiatives for the rehabilitation and management of vernacular settlements in Oman: a phenomenon in the making
Authors: Naima Benkari 
Published: December 2021

AbstractOnce abandoned for more than three decades, vernacular settlements in Oman are now being progressively reinvested in to foster the country’s heritage tourism sector. The present research focuses on the emerging phenomenon of community-led initiatives for vernacular heritage rehabilitation and adaptive reuse in Oman. Through an examination of three case studies, its aim is to describe this process and its modes of action and discuss its effects on vernacular settlement transformations. A mixed research methodology was designed to include (A) analyses of relevant primary and secondary data, (B) documented onsite observations, (C) interviews with local community representatives and key players in the operations of rehabilitation, and (D) extractions and analyses of quantitative data from a hotel booking website.The research sheds light on unsuspected interrelations within and between the projects being implemented in these settlements and their operating modes. It reveals the focal role of a local community in a kind of ‘bottom-up’ management of its built heritage, coupled with a ‘horizontal cooperation’ between the three initiatives studied in this research. Moreover, it shows that a heavily centralised and top-down policy for the field of heritage conservation and management is among the main obstacles that hinder such initiatives. Furthermore, community-led operations of vernacular heritage rehabilitation are being undertaken under insufficient regulations in terms of land use, building restoration and adaptive reuse. In this context, the paper discusses some of the serious threats and concerns faced by such initiatives and proposes actionable solutions to mitigate these hindrances.
Isatis indigotica: from (ethno) botany, biochemistry to synthetic biology
Authors: Feng Jingxian , Huang Doudou , Yang Yingbo , Chen Junfeng , Qiu Shi , Lv Zongyou , Ma Xueqi , Li Yuanyu , Li Rongrong , Xiao Ying , Chen Wansheng 
Published: December 2021

AbstractIsatis indigotica Fort. (Chinese woad) is a species with an ancient and well-documented history as an indigo dye and medicinal plant. It is often confused with Isatis tinctoria L. (European woad), a medicinal plant in Europe. Here, the differences between I. indigotica and I. tinctoria are systematically described. The usage development history, clinical applications and pharmacological activities, and chemical components of I. indigotica are also summarized. Lignans, indole alkaloids, and their corresponding derivatives have been identified as the major active ingredients of I. indigotica and are associated with anti-viral, anti-inflammatory, anti-cancer, and other health-promoting activities. Notable progress has been made in understanding the biosynthetic pathway and regulation mechanism of lignans and indole alkaloids in I. indigotica, the results from which should facilitate the process of targeted metabolic engineering or synthetic biology. Moreover, multiple biotechnology methods such as polyploid breeding and genetic engineering have been used with I. indigotica to result in, for example, greater yields, higher levels of bioactive component accumulation, and enhanced stress tolerance to salt, drought, and insects. Some issues require additional analyses, and suggestions for future research on I. indigotica are also discussed.
PBPK Simulation-Based Evaluation of Ganciclovir Crystalluria Risk Factors: Effect of Renal Impairment, Old Age, and Low Fluid Intake
Authors: Scotcher Daniel , Galetin Aleksandra 
Published: December 2021

AbstractDosing guidance is often lacking for chronic kidney disease (CKD) due to exclusion of such patients from pivotal clinical trials. Physiologically based pharmacokinetic (PBPK) modelling supports model-informed dosing when clinical data are lacking, but application of these approaches to patients with impaired renal function is not yet at full maturity. In the current study, a ganciclovir PBPK model was developed for patients with normal renal function and extended to CKD population. CKD-related changes in tubular secretion were explored in the mechanistic kidney model and implemented either as proportional or non-proportional decline relative to GFR. Crystalluria risk was evaluated in different clinical settings (old age, severe CKD and low fluid intake) by simulating ganciclovir medullary collecting duct (MCD) concentrations. The ganciclovir PBPK model captured observed changes in systemic pharmacokinetic endpoints in mild-to-severe CKD; these trends were evident irrespective of assumed pathophysiological mechanism of altered active tubular secretion in the model. Minimal difference in simulated ganciclovir MCD concentrations was noted between young adult and geriatric populations with normal renal function and urine flow (1 mL/min), with lower concentrations predicted for severe CKD patients. High crystalluria risk was identified at reduced urine flow (0.1 mL/min) as simulated ganciclovir MCD concentrations exceeded its solubility (2.6–6 mg/mL), irrespective of underlying renal function. The analysis highlighted the importance of appropriate distribution of virtual subjects’ systems data in CKD populations. The ganciclovir PBPK model illustrates the ability of this translational tool to explore individual and combined effects of age, urine flow, and renal impairment on local drug renal exposure.
Graphical Abstract
The association between therapeutic plasma exchange and the risk of mortality among patients critically ill with COVID-19: a meta-analysis
Authors: Wardhani Shinta Oktya , Fajar Jonny Karunia , Soegiarto Gatot , Wulandari Laksmi , Maliga Helnida Anggun , Ilmawan Muhammad , Merysa Risna , Simamora Arlentina Bentivolia , Aini Qurrata , Noviantari Komang , Lestari Ayu Widya , Harnila Maria Yoheni , Syafi'i Imam , Djianzonie Jane Andrea Christiano , Siagian Nenci , Nining Sri , Hanim Risyda Zakiyah , Wahyuni Wahyuni , Aulia Fitri , Juliansyah Juliansyah , Mahmud Reflin , Tamara Fredo , Mahendra Aditya Indra , Wowor Amanda Cininta , Baladraf Fikri , Hadinata Ponda Hernest , Ikkeputri Adhityari , Nadya Hana , Kartini Dessy Aprilia , Husnah Milda , Nainu Firzan , Harapan Harapan 
Published: December 2021

Background: Cytokine storm has been widely known to contribute to the development of the critical condition in patients with coronavirus disease 2019 (COVID-19), and studies had been conducted to assess the potential aspect of cytokine storm elimination by performing therapeutic plasma exchange (TPE). However, contradictory findings were observed. The objective of this study was to assess the association between TPE and the reduction of mortality of critically ill COVID-19 patients. Methods: A meta-analysis was conducted by collecting data from PubMed, Scopus, and Web of Science. Data on the mortality rate of critically ill COVID-19 patients treated with TPE plus standard of care and that of patients treated with standard of care alone were analyzed using a Z test. Results: We included a total of four papers assessing the association between TPE and the risk of mortality among critically ill COVID-19 patients. Our findings suggested that critically ill COVID-19 patients treated with TPE had lower risk of mortality compared to those without TPE treatment. Conclusion: Our study has identified the potential benefits of TPE in reducing the risk of mortality among critically ill COVID-19 patients.
Validity of automated audiometry for hearing examination in patients with multidrug-resistant tuberculosis
Authors: Purnami Nyilo , Palandeng Rian W. , - Soedarsono , Arifianto Dhany , Moon In Seok 
Published: December 2021

Background: The objective of this study was to test the validity of automated audiometry as a method of hearing examination in patients with multidrug-resistant tuberculosis. Methods: This was a cross-sectional comparative study with a retrospective approach, using patient medical records. Patients with multidrug-resistant tuberculosis (MDR-TB) were recruited based-on medical records that met the inclusion and exclusion criteria at the Pulmonology outpatient unit, then referred to the Otorhinolaryngology outpatient unit of the Dr. Soetomo Academic Medical Center. The subjects’ hearing function was measured with two different devices (automated audiometer and conventional audiometer) before being given anti-tuberculosis drug therapy (aminoglycoside injection) as ototoxicity monitoring from July to December 2019 period. Sensitivity and specificity analysis was used to assess the validity of the test. Results: A total of 36 patients (72 ears) were included. The comparison test results using the Mann-Whitney test showed that there were significant differences between automated audiometry and conventional audiometry in both ears. Analysis values were: sensitivity 80-97%, specificity 37-96%, positive predictive value 74-98%, and negative predictive value 59-96%. Conclusions: Automated audiometry is valid for use as a method of hearing examination and monitoring in patients with multidrug-resistant tuberculosis.
Practical needs and considerations for refugees and other forcibly displaced persons with neurological disorders: Recommendations using a modified Delphi approach
Authors: Rezaei Shawheen , Sakadi Foksouna , Hiew Fu-Liong , Rodriguez-Leyva Ildefonso , Kruja Jera , Wasay Mohammad , Seidi Osheik AbuAsha , Abdel-Aziz Saad , Nafissi Shahriar , Mateen Farrah ,   Global Working Group for Refugees with Neurological Needs
Published: December 2021

Background: There are >70 million forcibly displaced people worldwide, including refugees, internally displaced persons, and asylum seekers. While the health needs of forcibly displaced people have been characterized in the literature, more still needs to be done globally to translate this knowledge into effective policies and actions, particularly in neurology. Methods: In 2020, a global network of published experts on neurological disease and refugees was convened. Nine physician experts from nine countries (2 low, 1 lower-middle income, 5 upper-middle, 1 high income) with experience treating displaced people originating from 18 countries participated in three survey and two discussion rounds in accordance with the Delphi method. Results: A consensus list of priority interventions for treating neurological conditions in displaced people was created, agnostic to cost considerations, with the ten highest ranking tests or treatments ranked as: computerized tomography scans, magnetic resonance imaging scans, levetiracetam, acetylsalicylic acid, carbamazepine, paracetamol, sodium valproate, basic blood tests, steroids and anti-tuberculous medication. The most important contextual considerations (100% consensus) were all economic and political, including the economic status of the displaced person’s country of origin, the host country, and the stage in the asylum seeking process. The annual cost to purchase the ten priority neurological interventions for the entire displaced population was estimated to be 220 million USD for medications and 4.2 billion USD for imaging and tests. Conclusions: A need for neuroimaging and anti-seizure medications for forcibly displaced people was emphasized. These recommendations could guide future research and investment in neurological care for forcibly displaced people.
Enrolment in clinical research at UCLH and geographically distributed indices of deprivation
Authors: Engleitner Holger , Jha Ashwani , Herron Daniel , Nelson Amy , Rees Geraint , McNally Nick , Williams Bryan , Nachev Parashkev 
Published: December 2021

Healthcare should be judged by its equity as well as its quality. Both aspects depend not only on the characteristics of service delivery but also on the research and innovation that ultimately shape them. Conducting a fully-inclusive evaluation of the relationship between enrolment in primary research studies at University College London Hospitals NHS Trust and indices of deprivation, here we demonstrate a quantitative approach to evaluating equity in healthcare research and innovation. We surveyed the geographical locations, aggregated into Lower Layer Super Output Areas (LSOAs), of all England-resident UCLH patients registered as enrolled in primary clinical research studies. We compared the distributions of ten established indices of deprivation across enrolled and non-enrolled areas within Greater London and within a distance-matched subset across England. Bayesian Poisson regression models were used to examine the relation between deprivation and the volume of enrolment standardized by population density and local disease prevalence. A total of 54593 enrolments covered 4401 LSOAs in Greater London and 10150 in England, revealing wide geographical reach. The distributions of deprivation indices were similar between enrolled and non-enrolled areas, exhibiting median differences from 0.26% to 8.73%. Across Greater London, enrolled areas were significantly more deprived on most indices, including the Index of Multiple Deprivation; across England, a more balanced relationship to deprivation emerged. Regression analyses of enrolment volumes yielded weak biases, in favour of greater deprivation for most indices, with little modulation by local disease prevalence. Primary clinical research at UCLH has wide geographical reach. Areas with enrolled patients show similar distributions of established indices of deprivation to those without, both within Greater London, and across distance-matched areas of England. We illustrate a robust approach to quantifying an important aspect of equity in clinical research and provide a flexible set of tools for replicating it across other institutions.
Investor Tastes, Corporate Behavior, and Stock Returns: An Analysis of Corporate Social Responsibility
Authors: Hwang Chuan Yang , Titman Sheridan , Wang Ying 
Published: December 2021

We classify institutions into socially responsible investors (SRI) and not socially responsible investors using the value weighted corporate social responsibility (CSR) scores of their portfolio holdings. We find that firms that exhibit increases in SRI ownership tend to increase future CSR scores. Our analysis of stock price responses to the revelation of SRI ownership changes indicates that the revelation of higher SRI ownership is associated with negative stock returns. These effects are particularly strong when we focus on SRI-activists, who tend to target firms with low CSR scores and lobby to increase them over time. These observations are consistent with the hypothesis that anticipated increases in CSR activities reduce firm values. This paper was accepted by David Simchi-Levi, finance.
Diagnostic and periprocedural discomfort in inflammatory bowel disease: a concept analysis using the Rodgers evolutionary method
Authors: Nistor Oana-Irina , Sawhney Monakshi , Wilson Rosemary 
Published: December 2021

Background: Inflammatory bowel disease (IBD) is a chronic, autoimmune gastrointestinal illness with a significant disease burden. The concept of discomfort in IBD lacks conceptual clarity. Aims: To analyse the concept of diagnostic and periprocedural discomfort in IBD and provide an understanding of its evolution, use in IBD research and implications for clinical practice through its attributes, antecedents, consequences and related terms. Methods: The Rodgers evolutionary concept analysis method guided this inductive approach. Findings: Seven journal articles, a dictionary, a thesaurus and one book were included in this analysis. The analysis yielded 12 surrogate terms, three attributes, five antecedents and one consequence. Diagnostic and periprocedural discomfort in IBD is an unpleasant, multidimensional and subjective experience, with biological, psychological or technical antecedents, which can occur independently of pain. Conclusion: Further research is required to enhance understanding of discomfort to improve the care of people living with IBD and their relationship with healthcare providers.
Noma (cancrum oris): A scoping literature review of a neglected disease (1843 to 2021)
Authors: Farley Elise , Mehta Ushma , Srour M. Leila , Lenglet Annick 
Published: December 2021

Background
Noma (cancrum oris) is an ancient but neglected and poorly understood preventable disease, afflicting the most disenfranchised populations in the world. It is a devastating and often fatal condition that requires urgent and intensive clinical and surgical care, often difficult to access as most cases of noma occur in resource-limited settings. We conducted a scoping review of the literature published on noma to understand the size and scope of available research on the disease and identify research gaps that need to be addressed to evolve our understanding of how to address this disease.

Methods
We searched 11 databases and collected primary peer reviewed articles on noma in all languages, the final search was conducted on 24th August 2021. The oldest manuscript identified was from 28th March 1843 and the most recently published manuscript was from 3rd June 2021. Search terms included cancrum oris and noma. Data was extracted using a standardised data extraction tool and key areas of interest were identified. The Preferred Reporting Items for Systemic review and Meta-Analyses requirements were followed.

Results
The review included 147 articles, the majority of the studies (n = 94, 64%) were case reports. Most manuscripts (n = 81, 55%) were published in the 2000s, 49 (33%) were from the 1900s and 17 (12%) from the 1800s. The main areas of interest identified were the history and epidemiology of the disease, noma’s clinical progression and aetiology, treatment regimens, mortality rates and the risk factors for the development of noma.

Conclusions
Noma has been reported in the literature for hundreds of years; however important gaps in our understanding of the disease remain. Future research should focus on determining the burden and distribution of disease; the true mortality rate, pathogenic cause(s) and the factors that influence prognosis and outcomes after treatment.
Nationwide screening for Fabry disease in unselected stroke patients
Authors: Tomek Aleš , Petra Reková , Paulasová Schwabová Jaroslava , Olšerová Anna , Škorňa Miroslav , Nevšímalová Miroslava , Šimůnek Libor , Herzig Roman , Fafejtová Štěpánka , Mikulenka Petr , Táboříková Alena , Neumann Jiří , Brzezny Richard , Sobolová Helena , Bartoník Jan , Václavík Daniel , Vachová Marta , Bechyně Karel , Havlíková Hana , Prax Tomáš , Šaňák Daniel , Černíková Irena , Ondečková Iva , Procházka Petr , Rajner Jan , Škoda Miroslav , Novák Jan , Škoda Ondřej , Bar Michal , Mikulík Robert , Dostálová Gabriela , Linhart Aleš ,   on behalf of the National Stroke Research Network, part of Czech Clinical Research Infrastructure Network (CZECRIN) and Czech Neurological Society, Cerebrovascular Section
Published: December 2021

Background and aims
Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by disease-associated variants in the alpha-galactosidase A gene (GLA). FD is a known cause of stroke in younger patients. There are limited data on prevalence of FD and stroke risk in unselected stroke patients.

Methods
A prospective nationwide study including 35 (78%) of all 45 stroke centers and all consecutive stroke patients admitted during three months. Clinical data were collected in the RES-Q database. FD was diagnosed using dried blood spots in a stepwise manner: in males—enzymatic activity, globotriaosylsphingosine (lyso-Gb3) quantification, if positive followed by GLA gene sequencing; and in females GLA sequencing followed by lyso-Gb3.

Results
986 consecutive patients (54% men, mean age 70 years) were included. Observed stroke type was ischemic 79%, transient ischemic attack (TIA) 14%, intracerebral hemorrhage (ICH) 7%, subarachnoid hemorrhage 1% and cerebral venous thrombosis 0.1%. Two (0.2%, 95% CI 0.02–0.7) patients had a pathogenic variant associated with the classical FD phenotype (c.1235_1236delCT and p.G325S). Another fourteen (1.4%, 95% CI 0.08–2.4) patients had a variant of GLA gene considered benign (9 with p.D313Y, one p.A143T, one p.R118C, one p.V199A, one p.R30K and one p.R38G). The index stroke in two carriers of disease-associated variant was ischemic lacunar. In 14 carriers of GLA gene variants 11 strokes were ischemic, two TIA, and one ICH. Patients with positive as compared to negative GLA gene screening were younger (mean 60±SD, min, max, vs 70±SD, min, max, P = 0.02), otherwise there were no differences in other baseline variables.

Conclusions
The prevalence of FD in unselected adult patients with acute stroke is 0.2%. Both patients who had a pathogenic GLA gene variant were younger than 50 years. Our results support FD screening in patients that had a stroke event before 50 years of age.
Prevalence and clinical course of upper airway respiratory virus infection in critically ill patients with hematologic malignancies
Authors: Lee Jongmin , Kim Seok Chan , Rhee Chin Kook , Lee Jaewoong , Lee Jong Wook , Lee Dong-Gun 
Published: December 2021

Background
The clinical significance of upper airway respiratory virus (RV) detection in patients with hematologic malignancies remains unclear. We aimed to investigate the association between upper airway RV detection and prognosis in critically ill patients with hematologic malignancies.

Methods
This retrospective observational study included 331 critically ill patients with hematologic malignancies who presented respiratory symptoms and their nasopharyngeal swab was tested using a multiplex PCR assay between January 2017 and December 2018. A logistic regression model was used to adjust for potential confounding factors in the association between assay positivity and in-hospital mortality.

Results
Among the 331 analyzed patients, RVs were detected in 29.0%. The overall mortality rates in the intensive care unit and hospital were 56.8% and 65.9%, respectively. Positive upper airway RV detection was associated with relapsed hematologic malignancies, higher level of C-reactive protein, and prior use of high dose steroids and anti-cancer chemotherapeutic drugs. Furthermore, it was independently associated with in-hospital mortality (adjusted odds ratio, 2.36; 95% confidence interval, 1.23 to 4.54). Among different RVs, parainfluenza virus was more prevalent among patients who died in the hospital than among those who survived (11.5% vs. 3.5%, P = 0.027).

Conclusions
RV detection in the upper respiratory tract was relatively common in our cohort and was significantly associated with a poor prognosis. Thus, it can be used as a predictor of prognosis. Moreover, RV presence in the upper respiratory tract should be examined in patients who have previously been prescribed with high dose corticosteroids and anti-cancer drugs.