bluuebunny/crossref_metadata_2025 huggingface dataset:
Managers in the publicly funded health services in China - characteristics and responsibilities
Authors: Liang Zhanming , Blackstock Felicity C. , Howard Peter , Liu Chaojie , Leggat Geoffrey , Ma Hongkun , Zhang Zhijun , Bartram Timothy
Published: August 2020

Background

Health service managers are integral to supporting the effective and efficient delivery of services. Understanding their competencies is essential to support reform and improvement of healthcare provision in China. This paper examines the characteristics and educational background of senior managers working in the community health and hospital sectors in China. We also examine their levels of commitment to continued professional development and continuous education.

Methods

A self-administered paper-based questionnaire was administered to 477 level I, II and III managers in community health services and public hospitals in China. The response rate was over 80%.

Results

Findings demonstrate significant differences in terms of educational background and commitment to ongoing professional development between the managers in China across levels of management, and between the community and hospital sectors. Hospital managers tend to be older; hospital managers at higher management levels are predominantly male but predominantly female in the community health services. A greater proportion of hospital managers have postgraduate qualifications. In addition, the participants identified specific management tasks that they considered important.

Conclusions

This is the first large scale study examining the educational background and commitment to professional development of senior health service managers in China. This study determined that there are differences between the demographics of managers in China across levels of management, but more importantly between the CHC and the hospital sectors. The identification of important managerial tasks will facilitate the development of appropriate education and training for Chinese healthcare managers. All sectors and levels reported the need for informal education focussed on the core roles of developing organisation image and public relations, improving quality and safety of service provision and provision of leadership. Further research to explore the underlying reasons for the above differences is needed to design appropriate professional development for China’s health services managers. In addition, the importance of managerial tasks across sectors and management levels requires further investigation.
The C-terminal region of the oxidoreductase MIA40 stabilizes its cytosolic precursor during mitochondrial import
Authors: Murschall Lena Maria , Gerhards Anne , MacVicar Thomas , Peker Esra , Hasberg Lidwina , Wawra Stephan , Langer Thomas , Riemer Jan
Published: August 2020

Background

The mitochondrial intermembrane space (IMS) is home to proteins fulfilling numerous essential cellular processes, particularly in metabolism and mitochondrial function. All IMS proteins are nuclear encoded and synthesized in the cytosol and must therefore be correctly targeted and transported to the IMS, either through mitochondrial targeting sequences or conserved cysteines and the mitochondrial disulfide relay system. The mitochondrial oxidoreductase MIA40, which catalyzes disulfide formation in the IMS, is imported by the combined action of the protein AIFM1 and MIA40 itself. Here, we characterized the function of the conserved highly negatively charged C-terminal region of human MIA40.

Results

We demonstrate that the C-terminal region is critical during posttranslational mitochondrial import of MIA40, but is dispensable for MIA40 redox function in vitro and in intact cells. The C-terminal negatively charged region of MIA40 slowed import into mitochondria, which occurred with a half-time as slow as 90 min. During this time, the MIA40 precursor persisted in the cytosol in an unfolded state, and the C-terminal negatively charged region served in protecting MIA40 from proteasomal degradation. This stabilizing property of the MIA40 C-terminal region could also be conferred to a different mitochondrial precursor protein, COX19.

Conclusions

Our data suggest that the MIA40 precursor contains the stabilizing information to allow for postranslational import of sufficient amounts of MIA40 for full functionality of the essential disulfide relay. We thereby provide for the first time mechanistic insights into the determinants controlling cytosolic surveillance of IMS precursor proteins.
Epidemiological and clinical features of pediatric COVID-19
Authors: Guo Cheng-Xian , He Li , Yin Ji-Ye , Meng Xiang-Guang , Tan Wei , Yang Guo-Ping , Bo Tao , Liu Jun-Ping , Lin Xin-Jian , Chen Xiang
Published: August 2020

Background

COVID-19 is an extremely severe infectious disease. However, few studies have focused on the epidemiological and clinical characteristics of pediatric COVID-19. This study conducted a retrospective review of the epidemiological and clinical features of COVID-19 in children.

Methods

A retrospective study was conducted on children with a definite diagnosis of COVID-19 in mainland China using the web crawler technique to collect anonymous COVID-19 updates published by local health authorities.

Results

Three hundred forty-one children aged 4 days to 14 years with a median age of 7 years were included. Sixty-six percent of pediatric patients were infected via family members with COVID-19. The median incubation period was 9 days (interquartile range, 6 to 13). Asymptomatic cases accounted for 5.9%, of which 30% had abnormal chest radiologic findings. A majority of pediatric COVID-19 cases showed mild to moderate clinical features, and only a few developed severe or critical diseases (0.6% and 0.3%, respectively). Fever (77.9%) and cough (32.4%) were the predominant presenting symptoms of pediatric COVID-19. The pediatric patients had fewer underlying diseases and complications than adults. The treatment modalities for pediatric COVID-19 patients were not as complex as those of adult COVID-19 patients. The overall prognosis of pediatric COVID-19 was benign with a decent recovery. The median time from onset to cure was 16 days (interquartile range, 13 to 21).

Conclusions

Compared to adults, COVID-19 in children has distinct features of epidemiology and clinical manifestations. The findings from this study might help to guide the development of measures to prevent and treat this ongoing global pandemic.

Trial registration

Chinese Clinical Trial Registry (chictr.org.cn) identifier: ChiCTR2000030464.
cjrABC-senB hinders survival of extraintestinal pathogenic E. coli in the bloodstream through triggering complement-mediated killing
Authors: Huang Wen-Chun , Liao Yi-Jyun , Hashimoto Masayuki , Chen Kuan-Fu , Chu Chishih , Hsu Po-Chuen , Wang Shuying , Teng Ching-Hao
Published: August 2020

Background

Extraintestinal pathogenicE. coli(ExPEC) is a common gram-negative organism causing various infections, including urinary tract infections (UTIs), bacteremia, and neonatal meningitis. ThecjrABC-senBgene cluster ofE. colicontributes to ExPEC virulence in the mouse model of UTIs. Consistently, the distribution ofcjrABC-senBis epidemiologically associated with human UTIs caused byE. coli.cjrABC-senB, which has previously been proposed to encode an iron uptake system, may facilitate ExPEC survival in the iron availability-restricted urinary tract. Given that the bloodstream is also an iron limited environment to invading bacteria, the pathogenic role ofcjrABC-senBin ExPEC bacteremia, however, remains to be investigated.

Methods

The ability of ExPEC RS218 strains with and withoutcjrABC-senBto survive in the mouse bloodstream and human serum was evaluated. Subsequently, the role of this gene cluster in the ExPEC interaction with the complement system was evaluated. Finally, the distribution ofcjrABC-senBin human clinicalE. coliisolates was determined by PCR. The frequency ofcjrABC-senBin bacteremia isolates that were not associated with UTIs (non-UTI bacteremia isolates) was compared with that in UTI-associated isolates and fecal isolates.

Results

Expression ofcjrABC-senBattenuated the survival of RS218 in the mouse bloodstream and human serum. ThecjrABC-senB-harboring strains triggered enhanced classical- and alternative-complement pathway activation and became more vulnerable to complement-mediated killing in serum.cjrAwas identified as the major gene responsible for the attenuated serum survival. ExpressingcjrABC-senBandcjrAincreased bacterial susceptibility to detergent and induced periplasmic protein leakage, suggesting that the expression of these genes compromises the integrity of the outer membrane of ExPEC. In addition, the frequency ofcjrABC-senBin non-UTI bacteremia isolates was significantly lower than that in UTI-associated isolates, while the frequencies in non-UTI bacteremia isolates and fecal isolates showed no significant difference. Consistently, this epidemiological investigation suggests thatcjrABC-senBdoes not contribute toE. colibacteremia in humans.

Conclusion

The contribution ofcjrABC-senBto the pathogenesis of ExPEC is niche dependent and contradictory because the genes facilitate ExPEC UTIs but hinder bacteremia. The contradictory niche-dependent characteristic may benefit the development of novel strategies againstE. coli-caused infections.
Zebrafish xenograft model of human lung cancer for studying the function of LINC00152 in cell proliferation and invasion
Authors: Shen Wenyi , Pu Juan , Sun Jing , Tan Bing , Wang Wei , Wang Lili , Cheng Jianmeng , Zuo Yangsong
Published: August 2020

Background

Numerous studies have shown that long noncoding RNAs play important roles in human cancer progression. Although zebrafish xenografts have recently become a novel in vivo model for human cancer research, whether such models can be used to study the function of long noncoding RNAs remains unknown.

Methods

In vitro studies validated the roles of LINC00152 in the proliferation and invasion of lung cancer cells. In vivo studies of zebrafish xenografts also confirmed these roles of LINC00152. In vivo confocal imaging was used to more accurately evaluate the function of LINC00152 in cell proliferation and migration. Pharmacological experiments were further performed to study the potential ability of LINC00152 downregulation combined with an EGFR inhibitor to treat tumors in cultured cells and the zebrafish xenograft model.

Results

Silencing of LINC00152 suppressed cell proliferation and invasion in SPCA1 and A549 lung cancer cell lines in vitro. In the zebrafish xenograft model, knockdown of LINC00152 reduced the proliferation and migration of lung cancer cells, as indicated by the two imaging methods at different magnifications. Moreover, the knockdown of LINC00152 enhanced the inhibition effect of afatinib for lung cancer progression in cultured cells and the zebrafish xenograft model.

Conclusion

Our study reveals the oncogenic roles and potential for LINC00152 to be a target for tumor treatment in lung cancer using zebrafish xenograft models, and the findings suggest that this model could be used for functional and application studies of human long noncoding RNAs in tumor biology.
Molecular characterization of Plasmodium falciparum DNA-3-methyladenine glycosylase
Authors: Pinthong Nattapon , Limudomporn Paviga , Vasuvat Jitlada , Adisakwattana Poom , Rattaprasert Pongruj , Chavalitshewinkoon-Petmitr Porntip
Published: August 2020

Background

The emergence of artemisinin-resistant malaria parasites highlights the need for novel drugs and their targets. Alkylation of purine bases can hinder DNA replication and if unresolved would eventually result in cell death. DNA-3-methyladenine glycosylase (MAG) is responsible for the repair of those alkylated bases. Plasmodium falciparum (Pf) MAG was characterized for its potential for development as an anti-malarial candidate.

Methods

Native PfMAG from crude extract of chloroquine- and pyrimethamine-resistant P. falciparum K1 strain was partially purified using three chromatographic procedures. From bio-informatics analysis, primers were designed for amplification, insertion into pBAD202/D-TOPO and heterologous expression in Escherichia coli of recombinant PfMAG. Functional and biochemical properties of the recombinant enzyme were characterized.

Results

PfMAG activity was most prominent in parasite schizont stages, with a specific activity of 147 U/mg (partially purified) protein. K1 PfMAG contained an insertion of AAT (coding for asparagine) compared to 3D7 strain and 16% similarity to the human enzyme. Recombinant PfMAG (74 kDa) was twice as large as the human enzyme, preferred double-stranded DNA substrate, and demonstrated glycosylase activity over a pH range of 4–9, optimal salt concentration of 100–200 mM NaCl but reduced activity at 250 mM NaCl, no requirement for divalent cations, which were inhibitory in a dose-dependent manner.

Conclusion

PfMAG activity increased with parasite development being highest in the schizont stages. K1 PfMAG contained an indel AAT (asparagine) not present in 3D7 strain and the recombinant enzyme was twice as large as the human enzyme. Recombinant PfMAG had a wide range of optimal pH activity, and was inhibited at high (250 mM) NaCl concentration as well as by divalent cations. The properties of PfMAG provide basic data that should be of assistance in developing anti-malarials against this potential parasite target.
Equality and poverty: views from managers and professionals from public services and household heads in the Belo Horizonte Metropolitan Area, Brazil
Authors: de França Viviane Helena , Modena Celina Maria , Confalonieri Ulisses Eugenio Cavalcanti
Published: August 2020

Background

Tackling poverty requires reconsideration of quantitative factors related to “who” is poor and by “how much” and qualitative factors addressing “what poverty means in these individuals’ lives”. Greater understanding is required concerning the types of access actually used by families in poverty in attempts to meet their basic needs. Poverty must be addressed based on the question: “Inequality of what?” It is in reflecting on the realities of such groups when their basic needs are not met that public policies can be improved and implemented with legitimate priorities. Objective: Describe coverage and access to public health, education and social assistance services and the related effects on the quality of life of families in extreme poverty.

Methods

An exploratory mixed methods study was conducted applying Amartya Sen’s “Basic Capability Equality” framework, with: 1) 27 interviews with managers and professionals from public services serving territories with extreme poverty; 2) Survey with a systematic proportionate stratified sample of 336 heads of households in extreme poverty from a total 2605 families. The resulting data was analyzed with thematic content analysis and descriptive statistics, respectively.

Results

The managers and professionals described the lives of families in extreme poverty with phrases such as, “These people suffer. Sadness weighs on their lives!” and “Depression is the most common illness”. Their precarious circumstances and inadequate access were cited as causes. Quality of life was considered bad or very bad by 41.4% of heads of households. A total income of less than one-third of the minimum wage was received by 56.9% of the sample. One or more people were unemployed in the family in 55.8% of cases. For 53.3% of heads of households, public services “did not meet any or few of their needs”. The main social determinants of health were described as: alcohol and drugs (68.8%); lack of good health care (60.7%); and absence of income/work (37.5%). The following were identified as solutions to improve their quality of life: (1) health (40.5%); (2) education (37.8%); and (3) employment (44.6%).

Conclusions

The social determinants of poverty and health must be addressed jointly through intersectoral public policies and egalitarian mechanisms that promote investment in social protection.
Allergic rhinitis and asthma symptoms in a real-life study of MP-AzeFlu to treat multimorbid allergic rhinitis and asthma
Authors: Price David , Klimek Ludger , Gálffy Gabriella , Emmeluth Melanie , Koltun Arkady , Kopietz Ferdinand , Nguyen Duc Tung , van Weissenbruch Ranny , Pohl Wolfgang , Kuhl Hans-Christian , Scadding Glenis , Mullol Joaquim
Published: August 2020

Background

Asthma affects up to nearly 40% of patients with allergic rhinitis (AR). Poor control of AR symptoms is associated with poor asthma control. The goal of this study was to evaluate the effect of AR treatment with MP-AzeFlu on symptoms of AR as well as symptoms of asthma.

Methods

This prospective study used a visual analog scale (VAS) to assess symptoms of AR and asthma before and after treatment with MP-AzeFlu (Dymista®; azelastine hydrochloride plus fluticasone propionate; 1 spray in each nostril twice daily for 2 weeks). Participants suffered from moderate-to-severe AR according to Allergic Rhinitis and its Impact on Asthma criteria, with acute AR symptoms (AR-VAS scores ≥ 50 mm) on inclusion day. In addition to symptom assessment, patients recorded the impact of AR symptoms on quality-of-life measures before, during, and at the conclusion of the treatment period (approximately 14 days). Patients self-reported change in frequency of their usage of asthma reliever medication on the last day of treatment.

Results

Of 1103 study participants, 267 (24.2%) had comorbid asthma. These participants reported using a mean of 5.1 puffs of asthma reliever medication in the week before treatment with MP-AzeFlu. A total of 81.8% of patients with comorbid asthma responded to AR therapy (AR-VAS < 50 mm on at least 1 study day). Among patients with AR and comorbid asthma, MP-AzeFlu was associated with improved VAS scores across all study parameters, including AR symptom severity, asthma symptom severity, sleep quality, daily work or school activities, daily social activities, and daily outdoor activities. Asthma symptom severity decreased from a mean of 48.9 mm to 24.1 mm on the VAS. Self-reported frequency of asthma reliever medication use was reduced for 57.6% of participants (n = 139/241).

Conclusion

MP-AzeFlu used to relieve AR symptoms was associated with reduced asthma symptom VAS scores and frequency of asthma reliever medication usage. Changes in overall symptoms of AR and asthma were correlated.
Retrospective quality of life study in patients with retroperitoneal sarcoma in an Asian population
Authors: Lim Hui Jun , Ong Chin-Ann Johnny , Skanthakumar Thakshayeni , Mak Lisa Yuen Hong , Wasudevan Seettha Devi , Tan Joey Wee-Shan , Chia Claramae Shulyn , Tan Grace Hwei Ching , Teo Melissa Ching Ching
Published: August 2020

Background

Retroperitoneal sarcoma represents 15% of sarcomas. The mainstay of treatment is surgery where a majority of patients require multi-visceral resections that may significantly impact their quality of life (QOL) following surgery. Studies in other cancers have shown that QOL may not be significantly impacted after radical or extensive surgery. However, there are limited studies examining the QOL specifically in patients with retroperitoneal sarcoma. In this pilot study, we retrospectively evaluated the QOL of patients with retroperitoneal sarcoma.

Methods

32 out of 90 patients who underwent surgical intervention for retroperitoneal sarcoma in National Cancer Centre Singapore from January 1999 to August 2018 who were alive and on follow-up were included in this study. EORTC-QLQ-C30 was administered to the patients.

Results

The median age of our patients was 59 years (range, 35–84), and median time from surgery to the implementation of questionnaire was 2.5 years (range, 0.05–9.6). Younger patients had significantly better differences in global health, physical and role functioning scores as compared to older individuals. Female patients reported higher global health, physical, emotional and social functioning scores than males. Patients who were more than 2 years post-surgery exhibited better QOL scores as compared to those who had more recent surgery. Our patients had comparable global health and functioning scores compared to a reference group of outpatient cancer patients at our institution.

Conclusions

Our pilot study investigating the QOL of patients with retroperitoneal sarcoma has shown that patients need to be followed up for at least 2 years following surgery to evaluate their QOL. In general, they achieved better functioning scores when compared with other cancer patients. These findings support the need for larger-scale prospective studies to further evaluate the QOL of these patients.
Correction to: Relationship of objectively measured physical activity and sedentary behaviour with health-related quality of life among breast cancer survivors
Authors: Nurnazahiah Ali , Shahril Mohd Razif , Syamimi Zakarai Nor , Ahmad Aryati , Sulaiman Suhaina , Lua Pei Lin
Published: August 2020

An amendment to this paper has been published and can be accessed via the original article.
Expression and clinical significance of LAG-3, FGL1, PD-L1 and CD8+T cells in hepatocellular carcinoma using multiplex quantitative analysis
Authors: Guo Mengzhou , Yuan Feifei , Qi Feng , Sun Jialei , Rao Qianwen , Zhao Zhiying , Huang Peixin , Fang Tingting , Yang Biwei , Xia Jinglin
Published: August 2020

Background

Fibrinogen-like protein 1 (FGL1)—Lymphocyte activating gene 3 (LAG-3) pathway is a promising immunotherapeutic target and has synergistic effect with programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1). However, the prognostic significance of FGL1-LAG-3 pathway and the correlation with PD-L1 in hepatocellular carcinoma (HCC) remain unknown.

Methods

The levels of LAG-3, FGL1, PD-L1 and cytotoxic T (CD8+T) cells in 143 HCC patients were assessed by multiplex immunofluorescence. Associations between the marker’s expression and clinical significances were studied.

Results

We found FGL1 and LAG-3 densities were elevated while PD-L1 and CD8 were decreased in HCC tissues compared to adjacent normal liver tissues. High levels of FGL1 were strongly associated with high densities of LAG-3+cells but not PD-L1. CD8+ T cells densities had positive correlation with PD-L1 levels and negative association with FGL1 expression. Elevated densities of LAG-3+cells and low levels of CD8+ T cells were correlated with poor disease outcome. Moreover, LAG-3+cells deteriorated patient stratification based on the abundance of CD8+ T cells. Patients with positive PD-L1 expression on tumor cells (PD-L1 TC+) tended to have an improved survival than that with negative PD-L1 expression on tumor cells (PD-L1 TC−). Furthermore, PD-L1 TC− in combination with high densities of LAG-3+cells showed the worst prognosis, and

PD-L1 TC+ patients with low densities of LAG-3+cells had the best prognosis.

Conclusions

LAG-3, FGL1, PD-L1 and CD8 have distinct tissue distribution and relationships with each other. High levels of LAG-3+cells and CD8+ T cells represent unfavorable and favorable prognostic biomarkers for HCC respectively.
Microstructural brain abnormalities in HIV+ individuals with or without chronic marijuana use
Authors: Wang Hannah A. , Liang Hua-Jun , Ernst Thomas M. , Oishi Kenichi , Chang Linda
Published: August 2020

Objective

Cognitive deficits and microstructural brain abnormalities are well documented in HIV-positive individuals (HIV+). This study evaluated whether chronic marijuana (MJ) use contributes to additional cognitive deficits or brain microstructural abnormalities that may reflect neuroinflammation or neuronal injury in HIV+.

Method

Using a 2 × 2 design, 44 HIV+ participants [23 minimal/no MJ users (HIV+), 21 chronic active MJ users (HIV + MJ)] were compared to 46 seronegative participants [24 minimal/no MJ users (SN) and 22 chronic MJ users (SN + MJ)] on neuropsychological performance (7 cognitive domains) and diffusion tensor imaging metrics, using an automated atlas to assess fractional anisotropy (FA), axial (AD), radial (RD), and mean (MD) diffusivities, in 18 cortical and 4 subcortical brain regions.

Results

Compared to SN and regardless of MJ use, the HIV+ group had lower FA and higher diffusivities in multiple white matter and subcortical structures (p < 0.001–0.050), as well as poorer cognition in Fluency (p = 0.039), Attention/Working Memory (p = 0.009), Learning (p = 0.014), and Memory (p = 0.028). Regardless of HIV serostatus, MJ users had lower AD in uncinate fasciculus (p = 0.024) but similar cognition as nonusers. HIV serostatus and MJ use showed an interactive effect on mean diffusivity in the right globus pallidus but not on cognitive function. Furthermore, lower FA in left anterior internal capsule predicted poorer Fluency across all participants and worse Attention/Working Memory in all except SN subjects, while higher diffusivities in several white matter tracts also predicted lower cognitive domain Z-scores. Lastly, MJ users with or without HIV infection showed greater than normal age-dependent FA declines in superior longitudinal fasciculus, external capsule, and globus pallidus.

Conclusions

Our findings suggest that, except in the globus pallidus, chronic MJ use had no additional negative influence on brain microstructure or neurocognitive deficits in HIV+ individuals. However, lower AD in the uncinate fasciculus of MJ users suggests axonal loss in this white matter tract that connects to cannabinoid receptor rich brain regions that are involved in verbal memory and emotion. Furthermore, the greater than normal age-dependent FA declines in the white matter tracts and globus pallidus in MJ users suggest that older chronic MJ users may eventually have lesser neuronal integrity in these brain regions.
A Japanese patient with ductal carcinoma of the prostate carrying an adenomatosis polyposis coli gene mutation: a case report
Authors: Umeda Kota , Kosaka Takeo , Nakamura Kohei , Takeda Toshikazu , Mikami Shuji , Nishihara Hiroshi , Oya Mototsugu
Published: August 2020

Background

Ductal carcinoma of the prostate is a histological subtype with a higher mortality than acinar adenocarcinoma. The number of cases is small and there are no treatment guidelines. We believe that this is the first report of ductal carcinoma of the prostate with an adenomatosis polyposis coli (APC) gene mutation in Japan.

Case presentation

An 85-year-old man presented with gross hematuria, and a papillary tumor in the prostatic urethra that was diagnosed as ductal carcinoma of the prostate following transurethral resection. Genetic analysis found an APC mutation with loss of heterozygosity. Immunostaining revealed focal nuclear translocation of β-catenin. APC mutations associated with loss of β-catenin degradation in the Wnt signaling pathway and result in over accumulation of β-catenin are thought to increase mortality. In this patient, β-catenin migrated into tumor cell nuclei.

Conclusion

To the best of our knowledge, this is the first report of ductal carcinoma of the prostate with an APC mutation in Japan. The development of a therapeutic Wnt inhibitor is discussed.
Phenotypic techniques and applications in fruit trees: a review
Authors: Huang Yirui , Ren Zhenhui , Li Dongming , Liu Xuan
Published: August 2020

Phenotypic information is of great significance for irrigation management, disease prevention and yield improvement. Interest in the evaluation of phenotypes has grown with the goal of enhancing the quality of fruit trees. Traditional techniques for monitoring fruit tree phenotypes are destructive and time-consuming. The development of advanced technology is the key to rapid and non-destructive detection. This review describes several techniques applied to fruit tree phenotypic research in the field, including visible and near-infrared (VIS–NIR) spectroscopy, digital photography, multispectral and hyperspectral imaging, thermal imaging, and light detection and ranging (LiDAR). The applications of these technologies are summarized in terms of architecture parameters, pigment and nutrient contents, water stress, biochemical parameters of fruits and disease detection. These techniques have been shown to play important roles in fruit tree phenotypic research.
Champions in context: which attributes matter for change efforts in healthcare?
Authors: Bonawitz Kirsten , Wetmore Marisa , Heisler Michele , Dalton Vanessa K. , Damschroder Laura J. , Forman Jane , Allan Katie R. , Moniz Michelle H.
Published: August 2020

Background

Research to date has focused on strategies and resources used by effective champions of healthcare change efforts, rather than personal characteristics that contribute to their success. We sought to identify and describe champion attributes influencing outcomes of healthcare change efforts. To examine attributes of champions, we used postpartum contraceptive care as a case study, because recommended services are largely unavailable, and implementation requires significant effort.

Methods

We conducted a comparative case study of the implementation of inpatient postpartum contraceptive care at 11 U.S. maternity hospitals in 2017–18. We conducted site visits that included semi-structured key informant interviews informed by the Consolidated Framework for Implementation Research (CFIR). Phase one analysis (qualitative content analysis using a priori CFIR codes and cross-case synthesis) showed that implementation leaders (“champions”) strongly influenced outcomes across sites. To understand champion effects, phase two inductive analysis included (1) identifying and elaborating key attributes of champions; (2) rating the presence or absence of each attribute in champions; and 3) cross-case synthesis to identify patterns among attributes, context, and implementation outcomes.

Results

We completed semi-structured interviews with 78 clinicians, nurses, residents, pharmacy and revenue cycle staff, and hospital administrators. All identified champions were obstetrician-gynecologists. Six key attributes of champions emerged: influence, ownership, physical presence at the point of change, persuasiveness, grit, and participative leadership style. These attributes promoted success by enabling champions to overcome institutional siloing, build and leverage professional networks, create tension for change, cultivate a positive learning climate, optimize compatibility with existing workflow, and engage key stakeholders. Not all champion attributes were required for success, and having all attributes did not guarantee success.

Conclusions

Effective champions appear to leverage six key attributes to facilitate healthcare change efforts. Prospective evaluations of the interactions among champion attributes, context, and outcomes may further elucidate how champions exert their effects.
Open heart surgery or echocardiographic transthoracic or percutaneous closure in secundum atrial septal defect: a developing approach in one Chinese hospital
Authors: Qi Hongwei , Zhao Jiangang , Tang Xiujie , Wang Xizheng , Chen Nan , Lv Wenqing , Bian Hong , Wang Shumin , Yuan Biao
Published: August 2020

Background

To study the clinical manifestations and advantages of open-heart surgery and echocardiographic transthoracic or percutaneous closure with secundum atrial septal defect (ASD). The surgeon’s learning curve was also analyzed.

Methods

In all, 115 consecutive patients with ASD from May 2013 to May 2019 were enrolled. According to the operative procedure, patients were divided into three groups: group one (open repair group) (n = 24), where patients underwent ASD repair (ASDR) under cardiopulmonary bypass (CPB); group two (closed surgical device closure group) (n = 69), where patients (six patients ≤1 y and sixteen ≤10 kg) underwent transthoracic ASD occlusion under transesophageal echocardiographic (TEE) guidance; and group three (transcatheter occlusion group) (n = 22), where patients underwent percutaneous ASD occlusion under echocardiography. The clinical features and results of each group were analyzed. All patients were telephonically followed-up after 3 months.

Results

All the three methods treating ASD were successfully performed in our hospital. It was also a typical developing history of congenital heart disease (CHD) surgery in China. One patient in the group two was transferred to emergency surgery for occluder retrieval and CPB-ASDR. Eight patients experienced failed transthoracic or percutaneous occlusion, two of whom underwent unsuccessful percutaneous closure at another hospital. Two patients each in the groups two and three were intraoperatively converted to CPB-ASDR. Two patient in the group three was converted to transthoracic occlusion surgery. All patients were discharged without any residual shunt. The three-month follow-up also did not show any residual shunt and occluder displacement.

Conclusion

In low-weight, infants, or huge ASDs with suitable rim for device occlusion, transthoracic ASD closure was successfully performed. Based on knowledge of ASD anatomy and skilled transthoracic occlusion of ASD, surgeons can perform percutaneous occlusion of ASD under echocardiographic guidance.
Cyclin-dependent kinases and rare developmental disorders
Authors: Colas Pierre
Published: August 2020

Extensive studies in the past 30 years have established that cyclin-dependent kinases (CDKs) exert many diverse, important functions in a number of molecular and cellular processes that are at play during development. Not surprisingly, mutations affecting CDKs or their activating cyclin subunits have been involved in a variety of rare human developmental disorders. These recent findings are reviewed herein, giving a particular attention to the discovered mutations and their demonstrated or hypothesized functional consequences, which can account for pathological human phenotypes. The review highlights novel, important CDK or cyclin functions that were unveiled by their association with human disorders, and it discusses the shortcomings of mouse models to reveal some of these functions. It explains how human genetics can be used in combination with proteome-scale interaction databases to loom regulatory networks around CDKs and cyclins. Finally, it advocates the use of these networks to profile pathogenic CDK or cyclin variants, in order to gain knowledge on protein function and on pathogenic mechanisms.
Modification of transcriptional factor ACE3 enhances protein production in Trichoderma reesei in the absence of cellulase gene inducer
Authors: Luo Yun , Valkonen Mari , Jackson Raymond E. , Palmer Jonathan M. , Bhalla Aditya , Nikolaev Igor , Saloheimo Markku , Ward Michael
Published: August 2020

Background

Trichoderma reesei is one of the best-known cellulolytic organisms, producing large quantities of a complete set of extracellular cellulases and hemicellulases for the degradation of lignocellulosic substances. Hence, T. reesei is a biotechnically important host and it is used commercially in enzyme production, of both native and foreign origin. Many strategies for producing enzymes in T. reesei rely on the cbh1 and other cellulase gene promoters for high-level expression and these promoters require induction by sophorose, lactose or other inducers for high productivity during manufacturing.

Results

We described an approach for producing high levels of secreted proteins by overexpression of a transcription factor ACE3 in T. reesei. We refined the ace3 gene structure and identified specific ACE3 variants that enable production of secreted cellulases and hemicellulases on glucose as a sole carbon source (i.e., in the absence of an inducer). These specific ACE3 variants contain a full-length Zn2Cys6 binuclear cluster domain at the N-terminus and a defined length of truncations at the C-terminus. When expressed at a moderate level in the fungal cells, the ACE3 variants can induce high-level expression of cellulases and hemicellulases on glucose (i.e., in the absence of an inducer), and further improve expression on lactose or glucose/sophorose (i.e., in the presence of an inducer). Finally, we demonstrated that this method is applicable to industrial strains and fermentation conditions, improving protein production both in the absence and in the presence of an inducer.

Conclusions

This study demonstrates that overexpression of ACE3 variants enables a high level of protein production in the absence of an inducer, and boosts protein production in the presence of an inducer. It is an efficient approach to increase protein productivity and to reduce manufacturing costs.
On the numerical solutions of two-dimensional scattering problems for an open arc
Authors: Li Hu , Huang Jin , Zeng Guang
Published: August 2020

For the scattering problems of acoustic wave for an open arc in two dimensions, we give a uniqueness and existence analysis via the single layer potential approach leading to a system of integral equations that contains a weakly singular operator. For its numerical solutions, we describe an $O(h^{3})$
O
(

h
3

)
order quadrature method based on the specific integral formula including convergence and stability analysis. Moreover, the asymptotic expansion of errors with odd power $O(h^{3})$
O
(

h
3

)
is got and the Richardson extrapolation algorithm (EA) is used to improve the accuracy of numerical solutions. The efficiency of the method is illustrated by a numerical example.
HDL Cholesterol Efflux Capacity is Impaired in Severe Short-Term Hypothyroidism Despite Increased HDL Cholesterol
Authors: van der Boom Trynke , Jia Congzhuo , Lefrandt Joop D , Connelly Margery A , Links Thera P , Tietge Uwe J F , Dullaart Robin P F
Published: August 2020

Context

Severe hypothyroidism has profound effects on lipoprotein metabolism including high-density lipoprotein (HDL) cholesterol elevations but effects on HDL function metrics are unknown.

Objective

To determine the impact of severe short-term hypothyroidism on HDL particle characteristics, HDL cholesterol efflux capacity (CEC), and HDL antioxidative capacity.

Design

Observational study with variables measured during severe short-term hypothyroidism (median TSH 81 mU/L) and after 20 weeks of thyroid hormone supplementation (median TSH 0.03 mU/L) (Netherlands Trial Registry ID 7228).

Setting

University hospital setting in The Netherlands.

Patients

Seventeen patients who had undergone a total thyroidectomy for differentiated thyroid carcinoma.

Main outcome measures

HDL particle characteristics (nuclear magnetic resonance spectrometry), CEC (human THP-1-derived macrophage foam cells and apolipoprotein B-depleted plasma), and HDL anti-oxidative capacity (inhibition of low-density lipoprotein oxidation).

Results

During hypothyroidism plasma total cholesterol, HDL cholesterol and apolipoprotein A-I were increased (P ≤ 0.001). HDL particle concentration was unchanged, but there was a shift in HDL subclasses toward larger HDL particles (P < 0.001). CEC was decreased (P = 0.035), also when corrected for HDL cholesterol (P < 0.001) or HDL particle concentration (P = 0.011). HDL antioxidative capacity did not change.

Conclusion

During severe short-term hypothyroidism CEC, an important antiatherogenic metric of HDL function, is impaired. HDL cholesterol and larger HDL particles are increased but HDL particle concentration is unchanged. Combined, these findings suggest that HDL quality and quantity are not improved, reflecting dysfunctional HDL in hypothyroidism.
Longitudinal Increases in Serum Insulin-like Factor 3 and Testosterone Determined by LC-MS/MS in Pubertal Danish Boys
Authors: Albrethsen Jakob , Ljubicic Marie Lindhardt , Juul Anders
Published: August 2020

Background

Serum concentrations of the peptide hormone insulin-like factor 3 (INSL3) is a candidate marker for improved distinction between constitutional delay of growth and puberty (CDGP) and permanent hypogonadotropic hypogonadism (HH) in boys.

Aim

To assess the possible diagnostic role of LC-MS/MS-based INSL3 measurements as a marker of imminent puberty by comparison with testosterone (T) and luteinizing hormone (LH) levels in serum longitudinally collected from 18 healthy boys throughout puberty.

Results

The first increase in serum LH was detected on average 4 months earlier, as compared with the first observed increases in INSL3 and T. When comparing the 2 testicular hormones only, we found that in 22% (4 of 18) of the boys the first increase in serum INSL3 was observed prior to the first observed increase in T, whereas in 44% (8 of 18) the first increase in T was observed before the first observed increase in INSL3. In the remaining 6 boys, the 2 testicular hormones showed the first increase at the same examination.

Conclusion

In some boys with delayed puberty, the first indication of testicular maturation may be detectable by observing serum INSL3. Further studies of LC-MS/MS determination of serum INSL3 in patients with CDGP and HH are warranted.
NC1-Peptide From Collagen α3 (IV) Chains in the Basement Membrane of Testes Regulates Spermatogenesis via p-FAK-Y407
Authors: Li Huitao , Liu Shiwen , Wu Siwen , Ge Renshan , Cheng C Yan
Published: August 2020

The blood–testis barrier (BTB) in the testis is an important ultrastructure to support spermatogenesis. This blood-tissue barrier undergoes remodeling at late stage VII to early stage IX of the epithelial cycle to support the transport of preleptotene spermatocytes across the BTB to prepare for meiosis I/II at the apical compartment through a mechanism that remains to be delineated. Studies have shown that NC1-peptide-derived collagen α3 (IV) chain in the basement membrane is a bioactive peptide that induces BTB remodeling. It also promotes the release of fully developed spermatids into the tubule lumen. Thus, this endogenously produced peptide coordinates these 2 cellular events across the seminiferous epithelium. Using an NC1-peptide complementary deoxyribonucleic acid (cDNA) construct to transfect adult rat testes for overexpression, NC1-peptide was found to effectively induce germ cell exfoliation and BTB remodeling, which was associated with a surge and activation of p-rpS6, the downstream signaling protein of mTORC1 and the concomitant downregulation of p-FAK-Y407 in the testis. In order to define the functional relationship between p-rpS6 and p-FAK-Y407 signaling to confer the ability of NC1-peptide to regulate testis function, a phosphomimetic (and thus constitutively active) mutant of p-FAK-Y407 (p-FAK-Y407E-MT) was used for its co-transfection, utilizing Sertoli cells cultured in vitro with a functional tight junction (TJ) barrier that mimicked the BTB in vivo. Overexpression of p-FAK-Y407E-MT blocked the effects of NC1-peptide to perturb Sertoli cell BTB function by promoting F-actin and microtubule cytoskeleton function, and downregulated the NC1-peptide-mediated induction of p-rpS6 activation. In brief, NC1-peptide is an important endogenously produced biomolecule that regulates BTB dynamics.
The King’s Two Anuses: Trans Feminism and Free Speech
Authors: Lavery Grace
Published: August 2020

“The King’s Two Anuses: Trans Feminism and Free Speech” critically examines the discourses of trans feminism and free speech absolutism as they have converged in a number of public controversies in the wake of the 2016 election of Donald Trump. It argues that the crisis of democratic institutions precipitated by that election revealed the surprising susceptibility of the dominant strains of critical and queer theory to cooptation by the far right and exposed the inadequacy of institutionalized rhetorics of trans affirmation, which generally comprise defenses of indeterminacy or gender ambivalence—the very conditions many trans people contest. Drawing on the late work of Michel Foucault and the private writings of Ernst Kantorowicz, “The King’s Two Anuses” articulates a critique of the Lacanian account of subjective sexuation (in the work of Judith Butler, Joan Copjec, and Slavoj Žižek), which it holds especially influential and especially inadequate to the task of accounting for the diversity and assertiveness of trans accounts of personhood.
Identification and rescue of a tRNA wobble inosine deficiency causing intellectual disability disorder
Authors: Ramos Jillian , Proven Melissa , Halvardson Jonatan , Hagelskamp Felix , Kuchinskaya Ekaterina , Phelan Benjamin , Bell Ryan , Kellner Stefanie M. , Feuk Lars , Thuresson Ann-Charlotte , Fu Dragony
Published: August 2020

The deamination of adenosine to inosine at the wobble position of tRNA is an essential post-transcriptional RNA modification required for wobble decoding in bacteria and eukaryotes. In humans, the wobble inosine modification is catalyzed by the heterodimeric ADAT2/3 complex. Here, we describe novel pathogenic ADAT3 variants impairing adenosine deaminase activity through a distinct mechanism that can be corrected through expression of the heterodimeric ADAT2 subunit. The variants were identified in a family in which all three siblings exhibit intellectual disability linked to biallelic variants in the ADAT3 locus. The biallelic ADAT3 variants result in a missense variant converting alanine to valine at a conserved residue or the introduction of a premature stop codon in the deaminase domain. Fibroblast cells derived from two ID-affected individuals exhibit a reduction in tRNA wobble inosine levels and severely diminished adenosine tRNA deaminase activity. Notably, the ADAT3 variants exhibit impaired interaction with the ADAT2 subunit and alterations in ADAT2-dependent nuclear localization. Based upon these findings, we find that tRNA adenosine deaminase activity and wobble inosine modification can be rescued in patient cells by overexpression of the ADAT2 catalytic subunit. These results uncover a key role for the inactive ADAT3 deaminase domain in proper assembly with ADAT2 and demonstrate that ADAT2/3 nuclear import is required for maintaining proper levels of the wobble inosine modification in tRNA.
Knowledge Sharing in Alliances and Alliance Portfolios
Authors: Arora Ashish , Belenzon Sharon , Patacconi Andrea
Published: August 2020

We develop a model of knowledge sharing in alliances and alliance portfolios. We show that, once the issue of encouraging effective collaboration is put center stage, many standard intuitions of the learning race view and alliance portfolio literature are overturned or qualified. Partners engage in learning races in some cases, but exhibit “altruistic” behaviors in other cases. They may reduce their own absorptive capacity or increase the transparency of their own operations to facilitate their partner’s learning. In alliance portfolios, we show that not all substitutability between alliance portfolio partners is bad. We distinguish between substitutability in implementation and substitutability in rival benefits and show that the latter is conducive to knowledge sharing. Our work contributes toward putting the literature on learning alliances on a more solid foundation by emphasizing the importance of commitments that leading firms can make to encourage collaboration.

This paper was accepted by David Simchi-Levi, business strategy.
Occurrence of Ants (Hymenoptera: Formicidae) in both Leaf Litter and Twigs in Atlantic Forest
Authors: Fernandes Tae Tanaami , Souza-Campana Débora Rodrigues , Silva Nathalia Sampaio , Silva Otávio Morais , Morini Maria Santina de Castro
Published: August 2020

Twigs in the litter derived from the fragmentation of tree branches form one microhabitat, where entire colonies of ants, both leaf litter and arboreal species, can be found. The objective was to survey ant species that are presente in both the leaf litter and twigs simultaneously. We describe the nest type, the social structure of the colonies and the trophic guild membership of these species. Samples were collected from 10 preserved fragments of Brazilian Atlantic forest. We used Berlese funnels to collect leaf litter ants and manual collection for twig ants. We recorded 80 ant species; 60 species were in leaf litter samples and 35 species were in twigs. Of the total species, only 15 (20%) occurred simultaneously in the leaf litter and in twigs. Of these species, Gnamptogenys striatula, Pheidole sarcina, P. sospes and Solenopsis sp. 2 were the most frequent among leaf litter dwellers, and Myrmelachista catharinae was the most common arboreal species. Most of these belonged to generalista and predator guilds, with “polydomous nests” and colonies monogynous.