bluuebunny/crossref_metadata_2025_split huggingface dataset:
The other side of the crisis: organizational flexibility in balancing Covid-19 and non-Covid-19 health-care services
Authors: Troisi Roberta , De Simone Stefania , Vargas Maria , Franco Massimo 
Published: August 2022

Abstract
Background
Many healthcare systems have been unable to deal with Covid-19 without influencing non-Covid-19 patients with pre-existing conditions, risking a paralysis in the medium term. This study explores the effects of organizational flexibility on hospital efficiency in terms of the capacity to deliver healthcare services for both Covid-19 and non-Covid-19 patients.

Method
Focusing on Italian health system, a two-step strategy is adopted. First, Data Envelope Analysis is used to assess the capacity of hospitals to address the needs of Covid-19 and non-Covid-19 patients relying on internal resource flexibility. Second, two panel regressions are performed to assess external organizational flexibility, with the involvement in demand management of external operators in the health-care service, examining the impact on efficiency in hospital capacity management.

Results
The overall response of the hospitals in the study was not fully effective in balancing the needs of the two categories of patients (the efficiency score is 0.87 and 0.58, respectively, for Covid-19 and non-Covid-19 patients), though responses improved over time. Furthermore, among the measures providing complementary services in the community, home hospitalization and territorial medicine were found to be positively associated with hospital efficiency (0.1290, p < 0.05 and 0.2985, p < 0.01, respectively, for non-Covid-19 and Covid-19 patients; 0.0026, p < 0.05 and 0.0069, p < 0.01, respectively, for non-Covid-19 and Covid-19). In contrast, hospital networks are negatively related to efficiency in Covid-19 patients (-0.1037, p < 0.05), while the relationship is not significant in non-Covid-19 patients.

Conclusions
Managing the needs of Covid-19 patients while also caring for other patients requires a response from the entire healthcare system. Our findings could have two important implications for effectively managing health-care demand during and after the Covid-19 pandemic. First, as a result of a naturally progressive learning process, the resource balance between Covid-19 and non-Covid-19 patients improves over time. Second, it appears that demand management to control the flow of patients necessitates targeted interventions that combine agile structures with decentralization. Finally, untested integration models risk slowing down the response, giving rise to significant costs without producing effective results.
Sex differences in adult asthma and COPD therapy: a systematic review
Authors: Rogliani Paola , Cavalli Francesco , Ritondo Beatrice Ludovica , Cazzola Mario , Calzetta Luigino 
Published: August 2022

Abstract
Background
Although asthma is more prevalent in women and the prevalence of COPD is increasing in women, the current international recommendations for the management and prevention of asthma and COPD provide no sex-related indication for the treatment of these diseases. Therefore, we systematically reviewed the evidence across literature on the sex-related effectiveness of asthma and COPD therapy.

Methods
This systematic review has been registered in PROSPERO and performed according to PRISMA-P. The PICO framework was applied for the literature search strategy: "patient problem” included adult patients suffering from asthma or COPD, “Intervention” regarded the pharmacological treatments for asthma or COPD, “Comparison” was vs. baseline, active controls, or placebo, “Outcome” was any difference sex-related in the effectiveness of interventions.

Results
In asthma 44% of the evidence reported that men responded better than women to the therapy, whereas this percentage was 28% in COPD. ICS was generally less effective in women than in men to treat asthma, and consistent evidence suggests that in asthmatic patients ICS/LABA/LAMA combination may be equally effective in both men and women. Due to the inconsistent available evidence, it is not possible to identify specific treatments whose effectiveness is related to sex difference in COPD patients.

Conclusions
There is a strong need of investigating the sex-related impact of asthma and COPD treatments. Pre-specified analyses in men and women should be planned in future trial protocols, a necessary condition that should be requested also by the regulatory agencies to overcome the anachronistic “one-size-fits-all” approach to therapeutics associated with suboptimal outcomes for patients.
Advances in the human skin microbiota and its roles in cutaneous diseases
Authors: Yang Yudie , Qu Lingbo , Mijakovic Ivan , Wei Yongjun 
Published: August 2022

AbstractSkin is the largest organ in the human body, and the interplay between the environment factors and human skin leads to some skin diseases, such as acne, psoriasis, and atopic dermatitis. As the first line of human immune defense, skin plays significant roles in human health via preventing the invasion of pathogens that is heavily influenced by the skin microbiota. Despite being a challenging niche for microbes, human skin is colonized by diverse commensal microorganisms that shape the skin environment. The skin microbiota can affect human health, and its imbalance and dysbiosis contribute to the skin diseases. This review focuses on the advances in our understanding of skin microbiota and its interaction with human skin. Moreover, the potential roles of microbiota in skin health and diseases are described, and some key species are highlighted. The prevention, diagnosis and treatment strategies for microbe-related skin diseases, such as healthy diets, lifestyles, probiotics and prebiotics, are discussed. Strategies for modulation of skin microbiota using synthetic biology are discussed as an interesting venue for optimization of the skin-microbiota interactions. In summary, this review provides insights into human skin microbiota recovery, the interactions between human skin microbiota and diseases, and the strategies for engineering/rebuilding human skin microbiota.
Impacts of stimulus parameters and configurations on motor cortex direct electrical stimulation using intrinsic optical imaging: a pilot study
Authors: Liu Long , Zhang Jiacheng , Sun Jie , Xu Kedi 
Published: August 2022

Abstract
Background
Motor cortex stimulation applied as a clinical treatment for neuropathic disorders for decades. With stimulation electrodes placed directly on the cortical surface, this neuromodulation method provides higher spatial resolution than other non-invasive therapies. Yet, the therapeutic effects reported were not in conformity with different syndromes. One of the main issues is that the stimulation parameters are always determined by clinical experience. The lack of understanding about how the stimulation current propagates in the cortex and various stimulation parameters and configurations obstruct the development of this method.

Methods
In this study, we investigated the effect of different stimulation configurations on cortical responses to motor cortical stimulations using intrinsic optical imaging.

Results
Our results showed that the cortical activation of electrical stimulation is not only related to the current density but also related to the propagation distance. Besides, stimulation configurations also affect the propagation of the stimulation current.

Conclusions
All these results provide preliminary experimental evidence for parameter and electrode configuration optimizations.
‘Why would we not want to keep everybody safe?’ The views of family members of people who use drugs on the implementation of drug consumption rooms in Scotland
Authors: Parkes Tessa , Price Tracey , Foster Rebecca , Trayner Kirsten M. A. , Sumnall Harry R. , Livingston Wulf , Perkins Andy , Cairns Beth , Dumbrell Josh , Nicholls James 
Published: August 2022

Abstract
Background
People who use drugs in Scotland are currently experiencing disproportionately high rates of drug-related deaths. Drug consumption rooms (DCRs) are harm reduction services that offer a safe, hygienic environment where pre-obtained drugs can be consumed under supervision. The aim of this research was to explore family member perspectives on DCR implementation in Scotland in order to inform national policy.

Methods
Scotland-based family members of people who were currently or formerly using drugs were invited to take part in semi-structured interviews to share views on DCRs. An inclusive approach to ‘family’ was taken, and family members were recruited via local and national networks. A convenience sample of 13 family members were recruited and interviews conducted, audio-recorded, transcribed, and analysed thematically using the Structured Framework Technique.

Results
Family members demonstrated varying levels of understanding regarding the existence, role, and function of DCRs. While some expressed concern that DCRs would not prevent continued drug use, all participants were in favour of DCR implementation due to a belief that DCRs could reduce harm, including saving lives, and facilitate future recovery from drug use. Participants highlighted challenges faced by people who use drugs in accessing treatment/services that could meet their needs. They identified that accessible and welcoming DCRs led by trusting and non-judgemental staff could help to meet unmet needs, including signposting to other services. Family members viewed DCRs as safe environments and highlighted how the existence of DCRs could reduce the constant worry that they had of risk of harm to their loved ones. Finally, family members emphasised the challenge of stigma associated with drug use. They believed that introduction of DCRs would help to reduce stigma and provide a signal that people who use drugs deserve safety and care.

Conclusions
Reporting the experience and views of family members makes a novel and valuable contribution to ongoing public debates surrounding DCRs. Their views can be used to inform the implementation of DCRs in Scotland but also relate well to the development of wider responses to drug-related harm and reduction of stigma experienced by people who use drugs in Scotland and beyond.
An avoidable crisis
Authors: Matheson Catriona , Robertson Roy 
Published: August 2022

AbstractIn Scotland drug policy and consequently the progress of evidence-based treatment options has been struggling for many years. Political inaction is brought about by a complex chain of legal and operational obstructions with local authorities deferring to national Government which in turn is paralysed by international convention. Scotland represents a case study demonstrating the adverse consequences of management by non medical requirements rather than implementation of a clinically proven progressive policy. The difficulty of translating theory and evidence into practice is acknowledged but suggestions are made for pragmatic and humanitarian initiatives.
lncRNA-AC079061.1/VIPR1 axis may suppress the development of hepatocellular carcinoma: a bioinformatics analysis and experimental validation
Authors: Lin Xia-Hui , Zhang Dan-Ying , Liu Zhi-Yong , Tang Wen-qing , Chen Rong-Xin , Li Dong-ping , Weng Shuqiang , Dong Ling 
Published: August 2022

Abstract
Background
Hepatocellular carcinoma (HCC) is one of the most malignant tumors to threaten human life, and the survival rate remains low due to delayed diagnosis. Meanwhile, lncRNAs have great potential for application in tumor prognosis, therefore relevant research in hepatocellular carcinoma is indispensable.

Methods
Based on the EZH2 expression, the differentially expressed lncRNAs DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) were identified in hepatocellular carcinoma by using the TCGA database. Bioinformatics technology was utilized to determine the effect of key genes in HCC progression. The methylation and immune infiltration analyses were performed to explore the underlying function of hub genes. Finally, cellular function experiments were performed to investigate the association between identified genes and biological phenotypes in HCC.

Results
lncRNA-AC079061.1, hsa-miR-765, and VIPR1 were identified as independent factors that affect the prognosis of hepatocellular carcinoma. The immune infiltration analyses revealed that lncRNA-AC079061.1 can alter the immune microenvironment and thus inhibit the development of HCC by regulating the expression of an immune-related gene (VIPR1). Methylation analyses demonstrated that VIPR1 expression is negatively related to the methylation level in HCC. Experimental results suggested that lncRNA-AC079061.1 and VIPR1 were frequently downregulated in HCC cells, while hsa-miR-765 was significantly upregulated. Moreover, the lncRNA-AC079061.1/VIPR1 axis suppressed the proliferation and invasion of HCC cells.

Conclusion
The present study identified the lncRNA-AC079061.1/VIPR1 axis as a novel biomarker that inhibited the proliferation and invasion of hepatocellular carcinoma, affecting the ultimate disease outcome.
Probiotics ameliorate IgA nephropathy by improving gut dysbiosis and blunting NLRP3 signaling
Authors: Tan Jiaxing , Dong Lingqiu , Jiang Zheng , Tan Li , Luo Xinyao , Pei Gaiqin , Qin Aiya , Zhong Zhengxia , Liu Xiang , Tang Yi , Qin Wei 
Published: August 2022

Abstract
Background
Recently, a few studies have indicated a relationship between the gut microbiota and IgA nephropathy (IgAN). Whether the gut microbiota participates in the pathogenesis of IgAN and whether probiotics are effective in treating IgAN are still controversial. Therefore, this study aimed to identify the differences in the structure of the gut microbiota between IgAN and controls and to evaluate the efficacy and mechanism of probiotics in the treatment of IgAN.

Methods
To address this question, 35 IgAN patients and 25 healthy volunteers were enrolled, and a mouse IgAN model was also constructed. The stool microbes were analyzed by 16S rRNA high-throughput sequencing to identify the differential strains between IgAN and healthy controls. The impact of probiotics on the structure of the intestinal flora and the efficacy of the probiotics in the treatment of IgAN were evaluated.

Results
Although the microflora structure of mice and humans was not the same, both patients and mice with IgAN exhibited gut microbiota dysbiosis, with all subjects presenting an evident decrease in Bifidobacterium levels. The Bifidobacterium proportion was negatively correlated with proteinuria and hematuria levels, indicating that the decreased Bifidobacterium abundance could be related to IgAN severity. Probiotic treatment containing Bifidobacterium in IgAN mice could significantly alleviate gut dysbiosis, specifically by increasing the proportion of beneficial bacteria and reducing the abundance of potentially pathogenic bacteria. Moreover, both probiotics and their metabolites, short-chain fatty acids (SCFAs), could attenuate IgAN clinicopathological manifestations by inhibiting the NLRP3/ASC/Caspase 1 signaling pathway.

Conclusions
Supplementation with probiotics mainly containing Bifidobacterium could markedly improve gut dysbiosis in IgAN. Moreover, both probiotics and their SCFA metabolites could attenuate the clinicopathological manifestations of IgAN by inhibiting the NLRP3/ASC/Caspase 1 signaling pathway. Therefore, probiotics have potential as an adjunctive therapy for IgAN.
Membrane transporters control cerebrospinal fluid formation independently of conventional osmosis to modulate intracranial pressure
Authors: Oernbo Eva K. , Steffensen Annette B. , Razzaghi Khamesi Pooya , Toft-Bertelsen Trine L. , Barbuskaite Dagne , Vilhardt Frederik , Gerkau Niklas J. , Tritsaris Katerina , Simonsen Anja H. , Lolansen Sara D. , Andreassen Søren N. , Hasselbalch Steen G. , Zeuthen Thomas , Rose Christine R. , Kurtcuoglu Vartan , MacAulay Nanna 
Published: August 2022

Abstract
Background
Disturbances in the brain fluid balance can lead to life-threatening elevation in the intracranial pressure (ICP), which represents a vast clinical challenge. Nevertheless, the details underlying the molecular mechanisms governing cerebrospinal fluid (CSF) secretion are largely unresolved, thus preventing targeted and efficient pharmaceutical therapy of cerebral pathologies involving elevated ICP.

Methods
Experimental rats were employed for in vivo determinations of CSF secretion rates, ICP, blood pressure and ex vivo excised choroid plexus for morphological analysis and quantification of expression and activity of various transport proteins. CSF and blood extractions from rats, pigs, and humans were employed for osmolality determinations and a mathematical model employed to determine a contribution from potential local gradients at the surface of choroid plexus.

Results
We demonstrate that CSF secretion can occur independently of conventional osmosis and that local osmotic gradients do not suffice to support CSF secretion. Instead, the CSF secretion across the luminal membrane of choroid plexus relies approximately equally on the Na+/K+/2Cl− cotransporter NKCC1, the Na+/HCO3− cotransporter NBCe2, and the Na+/K+-ATPase, but not on the Na+/H+ exchanger NHE1. We demonstrate that pharmacological modulation of CSF secretion directly affects the ICP.

Conclusions
CSF secretion appears to not rely on conventional osmosis, but rather occur by a concerted effort of different choroidal transporters, possibly via a molecular mode of water transport inherent in the proteins themselves. Therapeutic modulation of the rate of CSF secretion may be employed as a strategy to modulate ICP. These insights identify new promising therapeutic targets against brain pathologies associated with elevated ICP.
Cowpea speed breeding using regulated growth chamber conditions and seeds of oven-dried immature pods potentially accommodates eight generations per year
Authors: Edet Offiong Ukpong , Ishii Takayoshi 
Published: August 2022

Abstract
Background
Cowpea is a dryland crop with potential to improve food security in sub-Saharan Africa, where it is mostly produced and consumed. Contemporary plant improvement technologies, including genome editing, marker-assisted selection, and optimized transformation protocols, are being deployed to improve cowpea characteristics. Integrating speed breeding with these technologies would accelerate genetic gain in cowpea breeding. There are established speed breeding protocols for other important legumes, such as soybean, peanut, and chickpea, but none has been previously reported for cowpea.

Results
With the aid of regulated growth conditions in two different chamber types, as well as the cultivation of new plant generations from seeds of oven-dried immature pods, we developed and validated, for the first time, an efficient speed breeding protocol that accommodates approximately seven to eight breeding generations per year for 3 cowpea genotypes. The 3 cowpea genotypes were evaluated under controlled growth conditions in light-emitting diode and metal halide lamp chambers to determine the effect of CO2 supplementation on flowering and maturation durations, optimum conditions for plant growth, cross pollination, and pod development. Elevated CO2 concentration had no influence on either flowering time or pod development. Adequate temperature, relative humidity and light intensity improved plant development and the rate of successful hand pollination, and cultivating seeds of 11-day-old immature pods oven-dried at 39 °C for 2 days resulted in at least a 62% reduction in the time between pollination and sowing of the next plant generation. The plants cultivated from seeds of the oven-dried immature pods showed no defect at any stage of development.

Conclusions
Using the speed breeding protocol developed in this study, cowpea breeding cycles can be increased from the traditional one cycle per year in the field to as many as 8 generations per year in regulated growth chamber conditions. This protocol has no special technical requirements; hence, it can be implemented in any standard growth chamber. This would fast-track development, testing, validation, and utilization of improved cowpea cultivars.
A novel knowledge-based prediction model for estimating an initial equivalent uniform dose in semi-auto-planning for cervical cancer
Authors: Tao Cheng , Liu Bo , Li Chengqiang , Zhu Jian , Yin Yong , Lu Jie 
Published: August 2022

Abstract
Background
We developed a novel concept, equivalent uniform length (EUL), to describe the relationship between the generalized equivalent uniform dose (EUD) and the geometric anatomy around a tumor target. By correlating EUL with EUD, we established two EUD–EUL knowledge-based (EEKB) prediction models for the bladder and rectum that predict initial EUD values for generating quality treatment plans.

Methods
EUL metrics for the rectum and bladder were extracted and collected from the intensity-modulated radiotherapy therapy (IMRT) plans of 60 patients with cervical cancer. The two EEKB prediction models were built using linear regression to establish the relationships between EULr and EUDr (EUL and EUD of rectum) and EULb, and EUDb (EUL and EUD of bladder), respectively. The EE plans were optimized by incorporating the predicted initial EUD parameters for the rectum and bladder with the conventional pinnacle auto-planning (PAP) initial dose parameters for other organs. The efficiency of the predicted initial EUD values were then evaluated by comparing the consistency and quality of the EE plans, PAP plans (based on default PAP initial parameters), and manual plans (designed manually by different dosimetrists) for a sample of 20 patients.

Results
Linear regression analyses showed a significant correlation between EUL and EUD (R2 = 0.79 and 0.69 for EUDb and EUDr, respectively). In a sample of 20 patients, the average bladder V40 and V50 derived from the EE plans were significantly lower (V40: 30.00 ± 5.76, V50: 14.36 ± 4.00) than the V40 and V50 values derived from manual plans (V40: 36.03 ± 8.02, V50: 19.02 ± 5.42). Compared with the PAP plans, the EE plans produced significantly lower average V30 and Dmean values for the bladder (V30: 50.55 ± 6.33, Dmean: 31.48 ± 1.97 Gy).

Conclusions
Our EEKB prediction models predicted reasonable initial EUD values for the rectum and bladder based on patient-specific geometric EUL values, thereby improving optimization and planning efficiency.
New progress in diagnosis and treatment of pulmonary arterial hypertension
Authors: Zhang Zai-qiang , Zhu Sheng-kui , Wang Man , Wang Xin-an , Tong Xiao-hong , Wan Jian-qiao , Ding Jia-wang 
Published: August 2022

AbstractPulmonary arterial hypertension (PAH) is a progressive disease. Although great progress has been made in its diagnosis and treatment in recent years, its mortality rate is still very significant. The pathophysiology and pathogenesis of PAH are complex and involve endothelial dysfunction, chronic inflammation, smooth muscle cell proliferation, pulmonary arteriole occlusion, antiapoptosis and pulmonary vascular remodeling. These factors will accelerate the progression of the disease, leading to poor prognosis. Therefore, accurate etiological diagnosis, treatment and prognosis judgment are particularly important. Here, we systematically review the pathophysiology, diagnosis, genetics, prognosis and treatment of PAH.