bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergistic optimisation of expression, folding, and secretion improves E. coli AppA phytase production in Pichia pastoris
Authors: Navone Laura , Vogl Thomas , Luangthongkam Pawarisa , Blinco Jo-Anne , Luna-Flores Carlos , Chen Xiaojing , von Hellens Juhani , Speight Robert 
Published: January 2021

Abstract
Background
Pichia pastoris (Komagataella phaffii) is an important platform for heterologous protein production due to its growth to high cell density and outstanding secretory capabilities. Recent developments in synthetic biology have extended the toolbox for genetic engineering of P. pastoris to improve production strains. Yet, overloading the folding and secretion capacity of the cell by over-expression of recombinant proteins is still an issue and rational design of strains is critical to achieve cost-effective industrial manufacture. Several enzymes are commercially produced in P. pastoris, with phytases being one of the biggest on the global market. Phytases are ubiquitously used as a dietary supplement for swine and poultry to increase digestibility of phytic acid, the main form of phosphorous storage in grains.

Results
Potential bottlenecks for expression of E. coli AppA phytase in P. pastoris were explored by applying bidirectional promoters (BDPs) to express AppA together with folding chaperones, disulfide bond isomerases, trafficking proteins and a cytosolic redox metabolism protein. Additionally, transcriptional studies were used to provide insights into the expression profile of BDPs. A flavoprotein encoded by ERV2 that has not been characterised in P. pastoris was used to improve the expression of the phytase, indicating its role as an alternative pathway to ERO1. Subsequent AppA production increased by 2.90-fold compared to the expression from the state of the AOX1 promoter.

Discussion
The microbial production of important industrial enzymes in recombinant systems can be improved by applying newly available molecular tools. Overall, the work presented here on the optimisation of phytase production in P. pastoris contributes to the improved understanding of recombinant protein folding and secretion in this important yeast microbial production host.
Malaria vectors diversity, insecticide resistance and transmission during the rainy season in peri-urban villages of south-western Burkina Faso
Authors: Soma Dieudonné Diloma , Poda Serge Bèwadéyir , Hien Aristide Sawdetuo , Namountougou Moussa , Sangaré Ibrahim , Sawadogo John Marie Emmanuel , Fournet Florence , Ouédraogo Georges Anicet , Diabaté Abdoulaye , Moiroux Nicolas , Dabiré Roch Kounbobr 
Published: January 2021

Abstract
Background
This study reports an updated description on malaria vector diversity, behaviour, insecticide resistance and malaria transmission in the Diébougou and Dano peri-urban areas, Burkina Faso.

Methods
Mosquitoes were caught monthly using CDC light traps and pyrethrum spray catches. Mosquitoes were identified using morphological taxonomic keys. PCR techniques were used to identify the species of the Anopheles gambiae complex and insecticide resistance mechanisms in a subset of Anopheles vectors. The Plasmodium sporozoite infection status and origins of blood meals of female mosquitoes were determined by ELISA methods. Larvae were collected, breed in the insectary and tested for phenotypic resistance against four insecticides using WHO bioassays.

Results
This study contributed to update the entomological data in two peri-urban areas of Southwest Burkina Faso. Anopheles populations were mostly anthropophilic and endophilic in both areas and exhibit high susceptibility to an organophosphate insecticide. This offers an alternative for the control of these pyrethroid-resistant populations. These data might help the National Malaria Control Programme for decision-making about vector control planning and resistance management.

Conclusions
This study contributed to update the entomological data in two peri-urban areas of Southwest Burkina Faso. Anopheles populations were mostly anthropophilic and endophilic in both areas and exhibit high susceptibility to an organophosphate insecticide. This offers an alternative for the control of these pyrethroid-resistant populations. These data might help the National Malaria Control Programme for decision-making about vector control planning and resistance management.
The impact of health insurance on poverty among rural older adults: an evidence from nine counties of western China
Authors: Zhai Shaoguo , Yuan Shuiping , Dong Quanfang 
Published: January 2021

Abstract
Background
Older adults are more prone to various diseases. Health insurance becomes effective mechanism to relieve financial burden when the insured is sick. In China, most older adults live in the countryside, and New Rural Cooperative Medical Scheme is a kind of health insurance system in rural areas. The relationship between New Rural Cooperative Medical Scheme and financial burden due to health expenditure of older adults in China was investigated. This paper aims at the impact of New Rural Cooperative Medical Scheme on the poverty among rural older adults.

Methods
This study employs Probit model and Tobit model to assess the impact of New Rural Cooperative Medical Scheme on alleviating poverty among rural older adults based on a survey in nine representative counties in western China.

Results
The findings show that diseases have significantly negative impact on rural elderly poverty. New Rural Cooperative Medical Scheme has impact on alleviating of the health-payment poverty due to catastrophic health expenditure, but the impact is limited. The impact of health insurance on poverty alleviation is greater for men, older adults aged between 60 to 69 and households in in economically poorer area than their counterparts.

Conclusions
This study show the relationship between New Rural Cooperative Medical Scheme and catastrophic health expenditure of older adults in China. The results draw policy attention to introduce different reimbursement expense ratios for different groups to alleviate them from poverty based on more comprehensive insurance packages.
Impact of antipsychotics in children and adolescents with autism spectrum disorder: a systematic review and meta-analysis
Authors:   On Behalf of the ISACA Guideline Working Group, D’Alò Gian Loreto , De Crescenzo Franco , Amato Laura , Cruciani Fabio , Davoli Marina , Fulceri Francesca , Minozzi Silvia , Mitrova Zuzana , Morgano Gian Paolo , Nardocci Franco , Saulle Rosella , Schünemann Holger Jens , Scattoni Maria Luisa 
Published: January 2021

Abstract
Background
The net health benefit of using antipsychotics in children and adolescents with ASD is unclear. This review was performed to provide the evidence necessary to inform the Italian national guidelines for the management of ASD.

Methods
We performed a systematic review of randomized controlled trials (RCTs) comparing antipsychotics versus placebo for the treatment of ASD in children and adolescents. For efficacy, acceptability and safety we considered outcomes evaluated by the guideline panel critical and important for decision-making. Continuous outcomes were analyzed by using standardized mean difference (SMD), and dichotomous outcomes by calculating the risk ratio (RR), with their 95% confidence interval (95% CI). Data were analyzed using a random effects model. We used the Cochrane tool to assess risk of bias of included studies. Certainty in the evidence of effects was assessed according to the GRADE approach.

Results
We included 21 RCTs with 1,309 participants, comparing antipsychotics to placebo. Antipsychotics were found effective on “restricted and repetitive interests and behaviors” (SMD − 0.21, 95% CI − 0.35 to − 0.07, moderate certainty), “hyperactivity, inattention, oppositional, disruptive behavior” (SMD − 0.67, 95% CI − 0.92 to − 0.42, moderate certainty), “social communication, social interaction” (SMD − 0.38, 95% CI − 0.59 to − 0.16, moderate certainty), “emotional dysregulation/irritability” (SMD − 0.71, 95% CI − 0.98 to − 0.43, low certainty), “global functioning, global improvement” (SMD − 0.64, 95% CI − 0.96 to − 0.33, low certainty), “obsessions, compulsions” (SMD − 0.30, 95% CI − 0.55 to − 0.06, moderate certainty). Antipsychotics were not effective on “self-harm” (SMD − 0.14, 95% CI − 0.58 to 0.30, very low certainty), “anxiety” (SMD − 0.38, 95% CI − 0.82 to 0.07, very low certainty). Antipsychotics were more acceptable in terms of dropout due to any cause (RR 0.61, 95% CI 0.48 to 0.78, moderate certainty), but were less safe in terms of patients experiencing adverse events (RR 1.19, 95% CI 1.07 to 1.32, moderate certainty), and serious adverse events (RR 1.07, 95% CI 0.48 to 2.43, low certainty).

Conclusions
Our systematic review and meta-analysis found antipsychotics for children and adolescents with ASD more efficacious than placebo in reducing stereotypies, hyperactivity, irritability and obsessions, compulsions, and in increasing social communication and global functioning. Antipsychotics were also found to be more acceptable, but less safe than placebo.
Psychiatric symptoms, risk, and protective factors among university students in quarantine during the COVID-19 pandemic in China
Authors: Sun Shufang , Goldberg Simon B. , Lin Danhua , Qiao Shan , Operario Don 
Published: January 2021

Abstract
Background
The COVID-19 pandemic has made unprecedented impact on the psychological health of university students, a population vulnerable to distress and mental health disorders. This study investigated psychiatric symptoms (anxiety, depression, and traumatic stress) during state-enforced quarantine among university students in China (N = 1912) through a cross-sectional survey during March and April 2020.

Results
Psychiatric symptoms were alarmingly prevalent: 67.05% reported traumatic stress, 46.55% had depressive symptoms, and 34.73% reported anxiety symptoms. Further, 19.56% endorsed suicidal ideation. We explored risk and protective factors of psychological health, including demographic variables, two known protective factors for mental health (mindfulness, perceived social support), four COVID-specific factors (COVID-19 related efficacy, perceived COVID-19 threat, perceived COVID-19 societal stigma, COVID-19 prosocial behavior) and screen media usage. Across symptom domains, mindfulness was associated with lower symptom severity, while COVID-19 related financial stress, perceived COVID-19 societal stigma, and perceived COVID-19 threat were associated with higher symptom severity. COVID-19 threat and COVID-19 stigma showed main and interactive effects in predicting all mental health outcomes, with their combination associated with highest symptom severity. Screen media device usage was positively associated with depression. Female gender and COVID-19 prosocial behavior were associated with higher anxiety, while COVID-19 self-efficacy associated with lower anxiety symptoms.

Conclusions
Findings suggest high need for psychological health promotion among university students during the COVID-19 pandemic and inform an ecological perspective on the detrimental role of stigma during an emerging infectious disease outbreak. Interventions targeting multi-level factors, such as promoting mindfulness and social support at individual and interpersonal levels while reducing public stigma about COVID-19, may be particularly promising. Attending to the needs of disadvantaged groups including those financially impacted by COVID-19 is needed.
Patellar resurfacing versus nonresurfacing in total knee arthroplasty: an updated meta-analysis of randomized controlled trials
Authors: Chen Kai , Dai Xiaoyu , Li Lidong , Chen Zhigang , Cui Haidong , Lv Shujun 
Published: January 2021

AbstractBackgroundWhether resurface the patella or not in total knee arthroplasty (TKA) was controversial. In 2013, we conducted a meta-analysis of randomized controlled trials (RTCs). After that, plenty of studies have been carried out, but there still existed a great deal of controversy. In order to update our previous study, we conducted this update meta-analysis to evaluate the efficacy of patellar resurfacing in TKA.MethodsDatabases were searched for RCTs comparing the outcomes of patellar resurfacing and nonresurfacing in TKA. Outcomes of knee relevant indicators were analysed. To see the short- and long-term effects, we calculated the data in total and divided the patients who were followed up for ≤ 3 years and ≥ 5 years into two subgroups as well.ResultsThirty-two trials assessing 6887 knees were eligible. There was a significant difference in terms of reoperation (in total and ≥ 5 years), Knee Society Score (KSS), function score (in total and ≥ 5 years) and noise. While no significant difference was found in the following items: reoperation (≤ 3 years), anterior knee pain (AKP), function score (≤ 3 years), range of motion (ROM), Oxford score, the Knee Injury and Osteoarthritis Outcome Score (KOOS), visual analogue score (VAS), Feller score, patellar tilt and the patients’ satisfaction.ConclusionsWe found that patellar resurfacing could reduce the occurrence of reoperation and noise after surgery, as well as increase the KSS and function score, while it might not influence the outcomes such as AKP, ROM, Oxford score, KOOS, VAS, Feller score, patellar tilt and the patients’ satisfaction. The results are different from our previous finding in the meta-analysis. In conclusion, we prefer patellar resurfacing in TKA.
Revised recommendations of the Italian Society of Pediatrics about the general management of Kawasaki disease
Authors: Marchesi Alessandra , Rigante Donato , Cimaz Rolando , Ravelli Angelo , Tarissi de Jacobis Isabella , Rimini Alessandro , Cardinale Fabio , Cattalini Marco , De Zorzi Andrea , Dellepiane Rosa Maria , Salice Patrizia , Secinaro Aurelio , Taddio Andrea , Palma Paolo , El Hachem Maya , Cortis Elisabetta , Maggio Maria Cristina , Corsello Giovanni , Villani Alberto 
Published: January 2021

AbstractAim of these revised recommendations for the general management of Kawasaki disease is to encourage its prompter recognition and warrant the most appropriate therapy, based on ascertained scientific data, raising awareness of the complications related to misdiagnosis or delayed treatment. A set of 20 synthetic operative statements is herein provided, including the definition of Kawasaki disease, its protean presentations, clinical course and seminal treatment modalities of all disease phases. The application of these recommendations should improve prognosis of Kawasaki disease and prevent the progression to permanent vascular abnormalities, thereby diminishing morbidity and mortality.
Effect of sex-specific differences on function of induced hepatocyte-like cells generated from male and female mouse embryonic fibroblasts
Authors: Ullah Imran , Shin Yurianna , Kim Yeongji , Oh Keon Bong , Hwang Seongsoo , Kim Young-Im , Lee Jeong Woong , Hur Tai-Young , Lee Seunghoon , Ock Sun A 
Published: January 2021

Abstract
Background
The liver is one of the vital organs involved in detoxification and metabolism. The sex-based differences between the functionality of male and female liver have been previously reported, i.e., male’s liver are good in alcohol clearance and lipid metabolism, while female’s liver are better in cholesterol metabolism. To date, studies on novel drug toxicity have not considered the sex-specific dimorphic nature of the liver. However, the use of hepatocyte-like cells to treat liver diseases has increased recently.

Methods
Mouse embryos were isolated from a pregnant female C57BL/6J mouse where mouse embryonic fibroblasts (MEFs) were isolated from back skin tissue of each embryo. MEFs were transduced with human transcription factors hHnf1α, hHnf4α, and hFoxa3 using the lentiviral system. The transduced MEFs were further treated with hepatocyte-conditioned media followed by its analysis through RT-qPCR, immunofluorescence, functional assays, and finally whole-transcriptome RNA sequencing analysis. For in vivo investigation, the mouse hepatocyte-like cells (miHep) were transplanted into CCl4-induced acute liver mouse model.

Results
In this study, we evaluated the sex-specific effect of miHep induced from male- and female-specific mouse embryonic fibroblasts (MEFs). We observed miHeps with a polygonal cytoplasm and bipolar nucleus and found that male miHeps showed higher mHnf4a, albumin secretion, and polyploidization than female miHeps. Transcriptomes from miHeps were similar to those from the liver, especially for Hnf4a of male miHeps. Male Cyps were normalized to those from females, which revealed Cyp expression differences between liver and miHeps. In both liver and miHeps, Cyp 4a12a and Cyp 4b13a/2b9 predominated in males and females, respectively. After grafting of miHeps, AST/ALT decreased, regardless of mouse sex.

Conclusion
In conclusion, activation of endogenic Hnf4a is important for generation of successful sex-specific miHeps; furthermore, the male-derived miHep exhibits comparatively enhanced hepatic features than those of female miHep.
p63 expression in human tumors and normal tissues: a tissue microarray study on 10,200 tumors
Authors: Steurer Stefan , Riemann Claudia , Büscheck Franziska , Luebke Andreas M. , Kluth Martina , Hube-Magg Claudia , Hinsch Andrea , Höflmayer Doris , Weidemann Sören , Fraune Christoph , Möller Katharina , Menz Anne , Fisch Margit , Rink Michael , Bernreuther Christian , Lebok Patrick , Clauditz Till S. , Sauter Guido , Uhlig Ria , Wilczak Waldemar , Dum David , Simon Ronald , Minner Sarah , Burandt Eike , Krech Rainer , Krech Till , Marx Andreas H. 
Published: January 2021

Abstract
Background
Tumor protein 63 (p63) is a transcription factor of the p53 gene family involved in differentiation of several tissues including squamous epithelium. p63 immunohistochemistry is broadly used for tumor classification but published data on its expression in cancer is conflicting.

Methods
To comprehensively catalogue p63 expression, tissue microarrays (TMAs) containing 12,620 tissue samples from 115 tumor entities and 76 normal tissue types were analyzed.

Results
p63 expression was seen in various normal tissues including squamous epithelium and urothelium. At least occasional weak p63 positivity could be detected in 61 (53%) of 115 different tumor types. The frequencies of p63 positivity was highest in squamous cell carcinomas irrespective of their origin (96–100%), thymic tumors (100%), urothelial carcinomas (81–100%), basal type tumors such as basal cell carcinomas (100%), and various salivary gland neoplasias (81–100%). As a rule, p63 was mostly expressed in cancers derived from p63 positive normal tissues and mostly not detectable in tumors derived from p63 negative cancers. However, exceptions from this rule occurred. A positive p63 immunostaining in cancers derived from p63 negative tissues was unrelated to aggressive phenotype in 422 pancreatic cancers, 160 endometrium cancers and 374 ovarian cancers and might be caused by aberrant squamous differentiation or represent stem cell properties. In 355 gastric cancers, aberrant p63 expression occurred in 4% and was linked to lymph node metastasis (p = 0.0208). Loss of p63 in urothelial carcinomas - derived from p63 positive urothelium - was significantly linked to advanced stage, high grade (p < 0.0001 each) and poor survival (p < 0.0001) and might reflect clinically relevant tumor dedifferentiation.

Conclusion
The high prevalence of p63 expression in specific tumor types makes p63 immunohistochemistry a suitable diagnostic tool. Loss of p63 expression might constitute a feature of aggressive cancers.
Impact of ICD-9-CM to ICD-10-CM coding transition on trauma hospitalization trends among young adults in 12 states
Authors: Sebastião Yuri V. , Metzger Gregory A. , Chisolm Deena J. , Xiang Henry , Cooper Jennifer N. 
Published: January 2021

Abstract
Background
We aimed to estimate the impact of the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) coding transition on traumatic injury-related hospitalization trends among young adults across a geographically and demographically diverse group of U.S. states.

Methods
Interrupted time series analyses were conducted using statewide inpatient databases from 12 states and including traumatic injury-related hospitalizations in adults aged 19–44 years in 2011–2017. Segmented regression models were used to estimate the impact of the October 2015 coding transition on external cause of injury (ECOI) completeness (percentage of hospitalizations with a documented ECOI code) and on population-level rates of injury-related hospitalizations by nature, intent, mechanism, and severity of injury.

Results
The transition to ICD-10-CM was associated with a drop in ECOI completion in the transition month (− 3.7%; P < .0001), but there was no significant change in the positive trend in ECOI completion from the pre- to post-transition periods. There were significant increases post-transition in the measured rates of hospitalization for traumatic brain injury (TBI), unintentional injury, mild injury (injury severity score (ISS) < 9), and injuries caused by drowning, firearms, machinery, other pedestrian, suffocation, and unspecified mechanism. Conversely, there were significant decreases in October 2015 in the rates of hospitalization for assault, injuries of undetermined intent, injuries of moderate severity (ISS 9–15), and injuries caused by fire/burn, other pedal cyclist, other transportation, natural/environmental, and other specified mechanism. A significant increase in the percentage of hospitalizations classified as resulting from severe injury (ISS > 15) was observed when the general equivalence mapping maximum severity method for converting ICD-10-CM codes to ICD-9-CM codes was used. State-specific results for the outcomes of ECOI completion and TBI-related hospitalization rates are provided in an online supplement.

Conclusions
The U.S. transition from ICD-9-CM to ICD-10-CM coding led to a significant decrease in ECOI completion and several significant changes in measured rates of injury-related hospitalizations by injury intent, mechanism, nature, and severity. The results of this study can inform the design and analysis of future traumatic injury-related health services research studies that use both ICD-9-CM and ICD-10-CM coded data.

Level of evidence
II (Interrupted Time Series)