bluuebunny/crossref_metadata_2025 huggingface dataset:
Demonstrating a systems approach for integrating disparate data streams to inform decisions on children’s environmental health
Authors: Hubal Elaine A Cohen , DeLuca Nicole M , Mullikin Ashley , Slover Rachel , Little John C , Reif David M
Published: February 2022

Background

The use of systems science methodologies to understand complex environmental and human health relationships is increasing. Requirements for advanced datasets, models, and expertise limit current application of these approaches by many environmental and public health practitioners.

Methods

A conceptual system-of-systems model was applied for children in North Carolina counties that includes example indicators of children’s physical environment (home age, Brownfield sites, Superfund sites), social environment (caregiver’s income, education, insurance), and health (low birthweight, asthma, blood lead levels). The web-based Toxicological Prioritization Index (ToxPi) tool was used to normalize the data, rank the resulting vulnerability index, and visualize impacts from each indicator in a county. Hierarchical clustering was used to sort the 100 North Carolina counties into groups based on similar ToxPi model results. The ToxPi charts for each county were also superimposed over a map of percentage county population under age 5 to visualize spatial distribution of vulnerability clusters across the state.

Results

Data driven clustering for this systems model suggests 5 groups of counties. One group includes 6 counties with the highest vulnerability scores showing strong influences from all three categories of indicators (social environment, physical environment, and health). A second group contains 15 counties with high vulnerability scores driven by strong influences from home age in the physical environment and poverty in the social environment. A third group is driven by data on Superfund sites in the physical environment.

Conclusions

This analysis demonstrated how systems science principles can be used to synthesize holistic insights for decision making using publicly available data and computational tools, focusing on a children’s environmental health example. Where more traditional reductionist approaches can elucidate individual relationships between environmental variables and health, the study of collective, system-wide interactions can enable insights into the factors that contribute to regional vulnerabilities and interventions that better address complex real-world conditions.
Treatment initiation among tuberculosis patients: the role of short message service (SMS) technology and Ward-based outreach teams (WBOTs)
Authors: Mwansa-Kambafwile Judith R. M. , Chasela Charles , Levin Jonathan , Ismail Nazir , Menezes Colin
Published: February 2022

Background

In South Africa, tuberculosis (TB) is a public health problem with treatment initiation failure rates varying between 14.9 and 25%. Lack of proper provider/patient communication on next steps after testing, not being aware that results are ready; and other competing priorities are some of the reasons for this failure. We aimed to assess the effectiveness of Short Message Service (SMS) technology and ward-based outreach teams (WBOTs) in improving TB treatment initiation. A 3-arm randomized controlled trial (Standard of care-SOC, SMS technology or WBOTs) was conducted between September 2018 and April 2020. Newly diagnosed TB patients randomly allocated to SMS and WBOTs groups were sent reminder messages (text message or paper slip respectively) that results were ready. Due to unforeseen challenges (financial and impact of the COVID 19 pandemic), implementation was only in two of the eight clinics planned.

Results

314 TB patients were assigned to one of three groups (SOC = 104, WBOTs = 105, and SMS = 105). Chi-square tests were used to compare proportions starting treatment (primary outcome). More patients in the SMS group (92/105; 88%) initiated treatment than in the SOC group (81/104; 78%), although this difference did not reach statistical significance (P = 0.062). The time to treatment initiation was significantly shorter in the SMS group than in the SOC group (P < 0.001). The proportions of patients initiated on treatment in the WBOTs group (45/62; 73%) and in the SOC group (44/61; 72%) were similar (P = 0.956). The times to treatment initiation for these two groups were also similar. The 3 group analysis yielded similar proportions initiated on treatment (P = 0.048 for SMS/SOC comparison and P = 0.956 for WBOTs/SOC comparison) but analysis of times to treatment initiation yielded some variations.

Conclusion

Reminder SMS messages sent to newly diagnosed TB patients improved the time to treatment initiation. Further research is required to show effect of the WBOTs intervention.

Trial registration

Retrospectively registered with the Pan African Clinical Trial Registry (PACTR202101914895981).

The trial was registered with the Pan African Clinical Trial Registry on 25 January, 2021 (ref: PACTR202101914895981; https://pactr.samrc.ac.za). The registration was retrospective due to an oversight. Nevertheless, the protocol details outlined in our ethics application were strictly adhered to.
Participation in scheduled asthma follow-up contacts and adherence to treatment during 12-year follow-up in patients with adult-onset asthma
Authors: Takala Jaana , Vähätalo Iida , Tuomisto Leena E. , Niemelä Onni , Ilmarinen Pinja , Kankaanranta Hannu
Published: February 2022

Background

Poor treatment compliance is a common problem in the treatment of asthma. To our knowledge, no previous long-term follow-up studies exist on how scheduled asthma follow-up contacts occur in primary health care (PHC) versus secondary care and how these contacts relate to adherence to medication and in participation to further scheduled asthma contacts. The aim of this study was to evaluate occurrence of scheduled asthma contacts and treatment compliance in PHC versus secondary care, and to identify the factors associated with non-participation to scheduled contacts.

Methods

Patients with new adult-onset asthma (n = 203) were followed for 12 years in a real-life asthma cohort of the Seinäjoki Adult Asthma Study (SAAS). The first contacts were mainly carried out in secondary care and therefore the actual follow-up time including PHC visits was 10 years.

Results

A majority (71%) of the patients had ≥ 2 scheduled asthma contacts during 10-year follow-up and most of them (79%) mainly in PHC. Patients with follow-up contacts mainly in PHC had better adherence to inhaled corticosteroid (ICS) medication during the whole 12-year period compared to patients in secondary care. In the study population, 29% of the patients had only 0–1 scheduled asthma contacts during the follow-up. Heavy alcohol consumption predicted poor participation in scheduled contacts.

Conclusions

Patients with mainly PHC scheduled asthma contacts were more adherent to ICS medication than patients in the secondary care. Based on our results it is necessary to pay more attention to actualization of asthma follow-up visits and systematic assessment of asthma patients including evaluation of alcohol consumption.

Trial registration Seinäjoki Adult Asthma Study is retrospectively registered at www.ClinicalTrials.gov with identifier number NCT02733016. Registered 11 April 2016.
Resolvin D1 inhibits the proliferation of osteoarthritis fibroblast-like synoviocytes through the Hippo-YAP signaling pathway
Authors: Su Siwei , Jiang Wenjun , Wang Xiaoying , Du Sen , Qi Jianhong , Jia Qingwei , Song Hongqiang
Published: February 2022

Objective

Osteoarthritis (OA) is a disease characterized by cartilage degradation and structural destruction. Resolvin D1 (RvD1), a specialized proresolving mediator (SPM) derived from omega-3 fatty acids, has been preliminarily proven to show anti-inflammatory and antiapoptotic effects in OA. However, the mechanisms of RvD1 in osteoarthritis fibroblast-like synoviocytes (OA-FLSs) need to be clarified.

Methods

Synovial and fibroblast-like synoviocytes were obtained from OA patients and healthy individuals. MTT and EdU assays were performed to determine cell cytotoxicity and proliferation. The protein expression levels of cyclin D1, cyclin B1, PCNA, p53, MMP-13, YAP, p-YAP, and LATS1 were detected by western blot analysis. The release levels of IL-1β were detected by ELISA. The cell cycle was assessed by flow cytometry. Immunofluorescence was used to detect the levels of YAP in OA-FLSs.

Results

RvD1 inhibited OA-FLS proliferation and reduced MMP-13 and IL-1β secretion in the concentrations of 20 nM and 200 nM. Furthermore, RvD1 induced G2 cell cycle arrest in OA-FLSs via the Hippo-YAP signaling pathway and promoted YAP phosphorylation. However, RvD1 had no effects on normal FLSs.

Conclusions

RvD1 inhibits OA-FLS proliferation by promoting YAP phosphorylation and protects chondrocytes by inhibiting the secretion of MMP-13 and IL-1β, providing an experimental basis for RvD1 treatment of OA.
Prevalence and predictive factors of complementary medicine use during the first wave of the COVID-19 pandemic of 2020 in the Netherlands
Authors: Mulder Louise T. C. , Busch Martine , Kristoffersen Agnete E. , Hök Nordberg Johanna , van der Werf Esther T.
Published: February 2022

Introduction

Major life changing events such as the COVID-19 pandemic may have major impact on one’s health and general well-being. This study aimed to determine the prevalence and predictive factors, including gender specific differences, of Complementary Medicine (CM) use (including CM consultations, self-care management and self-help techniques) during the first wave of the COVID-19 pandemic in 2020 in the Netherlands.

Methods

CM use was studied among a random representative sample (n = 1004) of the adult Dutch population using an online survey conducted from 22–27 May 2020. The survey included a modified version of I-CAM-Q and additional questions on demographic characteristics, reasons for CM use, perceived effectiveness and side effects.

Results

68.0% of the participants reported to have used CM (CM consultations (13.3%), self-management strategies (59.4%), self-help techniques (30.0%)). Most frequently reported reason of CM use was to improve general well-being (61.6%), prevention and/or treatment of COVID-19 was only reported by 10%. Perceived effectiveness of CM was high and number of experienced side effects low. Being a women, worried to get infected with COVID-19, higher education and living in northern/ middle region of the Netherlands were predictive factors to use CM.

Conclusions

In the Netherlands, specific groups (e.g. women/ highly educated) use CM, mainly to improve general wellbeing, and seem to benefit of it during the first months of the pandemic. The high perceived effectiveness and low reporting of side effects should encourage medical professionals and policy makers for more openness towards considering CM as being part of an integrative approach to public health in times life changing events occur.
Reimbursement decisions for medical services in Austria: an analysis of influencing factors for the hospital individual services catalogue between 2008 and 2020
Authors: Goetz Gregor , Panteli Dimitra , Busse Reinhard , Wild Claudia
Published: February 2022

Objectives

To (1) describe the (evidence-based) reimbursement process of hospital individual services, (2) evaluate the accordance between evidence-based recommendations and reimbursement decision of individual services and (3) elaborate potential aspects that play a role in the decision-making process in Austria.

Method

The reimbursement process is described based on selected relevant sources such as official documents. Evidence-based recommendations and subsequent reimbursement decisions for the annual maintenance of the hospital individual service catalogue in Austria between 2008 and 2020 were analysed using a mixed methods approach, encompassing descriptive statistics and a focus group with Austrian decision makers.

Results

118 evidence-based recommendations were analysed. There were 93 (78.8%) negative and 25 (21.2%) positive evidence-based recommendations. In total, 107 out of 118 evidence-based recommendations (90.1%) did not lead to a deviating reimbursement decision. We identified six aspects that may have played a role in the decision-making process for the annual maintenance of the hospital individual service catalogue, with clinical evidence being the most notable. Further aspects included quality assurance/organisational aspects (i.e., structural quality assurance), costs (if comparable to already existing medical services, not: cost-effectiveness), procedural aspects (e.g., if certain criteria for adoption have not been met formally through the proposals), “other countries” (i.e., taking into account how other countries decided) and situational aspects (such as the COVID-19 pandemic).

Conclusions

There is good accordance between evidence-based recommendations and reimbursement decisions regarding hospital individual services in Austria. Beyond clinical evidence, organisational aspects seem to be considered often with regard to quality assurance but costs do not appear to play a major role. The Austrian system has mechanisms in place that can restrict widespread adoption of novel hospital individual services with uncertain clinical benefits. Future studies could investigate how well these mechanisms work and how they compare to other health systems in Europe.
Source matters: a survey of cost variation for fecal immunochemical tests in primary care
Authors: Coury Jennifer , Ramsey Katrina , Gunn Rose , Judkins Jon , Davis Melinda
Published: February 2022

Background

Colorectal cancer (CRC) screening can improve health outcomes, but screening rates remain low across the US. Mailed fecal immunochemical tests (FIT) are an effective way to increase CRC screening rates, but is still underutilized. In particular, cost of FIT has not been explored in relation to practice characteristics, FIT selection, and screening outreach approaches.

Methods

We administered a cross-sectional survey drawing from prior validated measures to 252 primary care practices to assess characteristics and context that could affect the implementation of direct mail fecal testing programs, including the cost, source of test, and types of FIT used. We analyzed the range of costs for the tests, and identified practice and test procurement factors. We examined the distributions of practice characteristics for FIT use and costs answers using the non-parametric Wilcoxon rank-sum test. We used Pearson’s chi-squared test of association and interpreted a low p-value (e.g. < 0.05) as evidence of association between a given practice characteristic and knowing the cost of FIT or fecal occult blood test (FOBT).

Results

Among the 84 viable practice survey responses, more than 10 different types of FIT/FOBTs were in use; 76% of practices used one of the five most common FIT types. Only 40 practices (48%) provided information on FIT costs. Thirteen (32%) of these practices received the tests for free while 27 (68%) paid for their tests; median reported cost of a FIT was $3.04, with a range from $0.83 to $6.41 per test. Costs were not statistically significantly different by FIT type. However, practices who received FITs from manufacturer’s vendors were more likely to know the cost (p = 0.0002) and, if known, report a higher cost (p = 0.0002).

Conclusions

Our findings indicate that most practices without lab or health system supplied FITs are spending more to procure tests. Cost of FIT may impact the willingness of practices to distribute FITs through population outreach strategies, such as mailed FIT. Differences in the ability to obtain FIT tests in a cost-effective manner could have consequences for implementation of outreach programs that address colorectal cancer screening disparities in primary care practices.
Development of an efficient and precise adenine base editor (ABE) with expanded target range in allotetraploid cotton (Gossypium hirsutum)
Authors: Wang Guanying , Xu Zhongping , Wang Fuqiu , Huang Yuefan , Xin Yanfeng , Liang Sijia , Li Bo , Si Huan , Sun Lin , Wang Qiongqiong , Ding Xiao , Zhu Xiangqian , Chen Luo , Yu Lu , Lindsey Keith , Zhang Xianlong , Jin Shuangxia
Published: February 2022

Background

Base editors (BEs) display diverse applications in a variety of plant species such as Arabidopsis, rice, wheat, maize, soybean, and cotton, where they have been used to mediate precise base pair conversions without the collateral generation of undesirable double-stranded breaks (DSB). Studies of single-nucleotide polymorphisms (SNPs) underpinning plant traits are still challenging, particularly in polyploidy species where such SNPs are present in multiple copies, and simultaneous modification of all alleles would be required for functional analysis. Allotetraploid cotton has a number of homoeologous gene pairs located in the A and D sub-genomes with considerable SNPs, and it is desirable to develop adenine base editors (ABEs) for efficient and precise A-to-G single-base editing without DSB in such complex genome.

Results

We established various ABE vectors based on different engineered adenosine deaminase (TadA) proteins fused to Cas9 variants (dCas9, nCas9), enabling efficient A to G editing up to 64% efficiency on-target sites of the allotetraploid cotton genome. Comprehensive analysis showed that GhABE7.10n exhibited the highest editing efficiency, with the main editing sites specifically located at the position A5 (counting the PAM as positions 21–23). Furthermore, DNA and RNA off-target analysis of cotton plants edited with GhABE7.10n and GhABE7.10d by whole genome and whole-transcriptome sequencing revealed no DNA off-target mutations, while very low-level RNA off-target mutations were detected. A new base editor, namely GhABE7.10dCpf1 (7.10TadA + dCpf1), that recognizes a T-rich PAM, was developed for the first time. Targeted A-to-G substitutions generated a single amino acid change in the cotton phosphatidyl ethanolamine-binding protein (GhPEBP), leading to a compact cotton plant architecture, an ideotype for mechanized harvesting of modern cotton production.

Conclusions

Our data illustrate the robustness of adenine base editing in plant species with complex genomes, which provides efficient and precise toolkit for cotton functional genomics and precise molecular breeding.
Asprosin induces vascular endothelial-to-mesenchymal transition in diabetic lower extremity peripheral artery disease
Authors: You Mei , Liu Yushuang , Wang Bowen , Li Li , Zhang Hexuan , He Hongbo , Zhou Qing , Cao Tingbing , Wang Lijuan , Zhao Zhigang , Zhu Zhiming , Gao Peng , Yan Zhencheng
Published: February 2022

Background

Altered adipokine secretion in dysfunctional adipose tissue facilitates the development of atherosclerotic diseases including lower extremity peripheral artery disease (PAD). Asprosin is a recently identified adipokine and displays potent regulatory role in metabolism, but the relationship between asprosin and lower extremity PAD remains uninvestigated.

Methods

33 type 2 diabetes mellitus (T2DM) patients (DM), 51 T2DM patients with PAD (DM + PAD) and 30 healthy normal control (NC) volunteers were recruited and the blood samples were collected for detecting the circulatory asprosin level and metabolomic screening. RNA sequencing was performed using the aorta tissues from the type 2 diabetic db/db mice and human umbilical vein endothelial cells (HUVECs) were treated with asprosin to determine its impact on the endothelial-to-mesenchymal transition (EndMT).

Results

The circulating levels of asprosin in DM + PAD group were significantly higher than that of NC group and the DM group. Circulating asprosin level was remarkably negatively correlated with ankle-brachial index (ABI), even after adjusting for age, sex, body mass index (BMI) and other traditional risk factors of PAD. Logistic regression analysis revealed that asprosin is an independent risk factor for PAD and receiver-operator characteristic (ROC) curve determined a good sensitivity (74.5%) and specificity (74.6%) of asprosin to distinguish PAD. Data from metabolomics displayed a typical characteristics of de novo amino acid synthesis in collagen protein production by myofibroblasts in patients with PAD and activation of TGF-β signaling pathway appeared in the aortic tissue of db/db mice. Asprosin directly induces EndMT in HUVECs in a TGF-β-dependent manner as TGF-β signaling pathway inhibitor SB431542 erased the promotional effect of asprosin on EndMT.

Conclusions

Elevated circulatory asprosin level is an independent risk factor of lower extremity PAD and might serve as a diagnostic marker. Mechanistically, asprosin directly induces EndMT that participates in vascular injury via activation of TGF-β signaling pathway.

Trial registration This trial was registered at clinicaltrials.gov as NCT05068895
Identification of UAP1L1 as a critical factor for prostate cancer and underlying molecular mechanism in tumorigenicity
Authors: Wu Xing-cheng , Yu Yu-zhong , Zuo Yu-zhi , Song Xian-Lu , Zhou Zhi-en , Xiao Yu , Luo Dao-sheng , Yan Wei-gang , Zhao Shan-Chao
Published: February 2022

Background

Prostate cancer is the second most common cancer in men, and some new target genes are needed to predict the risk of prostate cancer progression and the treatment.

Methods

In this study, the effects of UAP1L1 (UAP1-like-1) on prostate cancer were investigated by detecting the proliferation, migration, invasion and apoptosis of prostate cancer cells in vitro using MTT, wound healing, Transwell and flow cytometry assay, and the tumor growth in vivo. The downstream genes and pathways of UAP1L1 were explored using Ingenuity Pathway Analysis (IPA), and screened by qRT-PCR and western blot. The effects of CDCA8 on prostate cancer cells were also verified in vitro, which was through detecting the change of proliferation, migration, invasion and apoptosis of prostate cancer cells after CDCA8 knockdown.

Results

The results indicated that UAP1L1 promoted the proliferation, migration and invasion of prostate cancer cells, which was inhibited by downregulating CDCA8. Furthermore, the promotion of CDCA8 knockdown on cell apoptosis was reduced when UAP1L1 was simultaneously overexpressed.

Conclusions

In conclusion, the results in this study revealed that UAP1L1 promoted the progression of prostate cancer through the downstream gene CDCA8.
In vivo detection of dysregulated choline metabolism in paclitaxel-resistant ovarian cancers with proton magnetic resonance spectroscopy
Authors: Lu Jing , Li Ying , Li Yong Ai , Wang Li , Zeng An Rong , Ma Xiao Liang , Qiang Jin Wei
Published: February 2022

Background

Chemoresistance gradually develops during treatment of epithelial ovarian cancer (EOC). Metabolic alterations, especially in vivo easily detectable metabolites in paclitaxel (PTX)-resistant EOC remain unclear.

Methods

Xenograft models of the PTX-sensitive and PTX-resistant EOCs were built. Using a combination of in vivo proton-magnetic resonance spectroscopy (1H-MRS), metabolomics and proteomics, we investigated the in vivo metabolites and dysregulated metabolic pathways in the PTX-resistant EOC. Furthermore, we analyzed the RNA expression to validate the key enzymes in the dysregulated metabolic pathway.

Results

On in vivo 1H-MRS, the ratio of (glycerophosphocholine + phosphocholine) to (creatine + phosphocreatine) ((GPC + PC) to (Cr + PCr))(i.e. Cho/Cr) in the PTX-resistant tumors (1.64 [0.69, 4.18]) was significantly higher than that in the PTX-sensitive tumors (0.33 [0.10, 1.13]) (P = 0.04). Forty-five ex vivo metabolites were identified to be significantly different between the PTX-sensitive and PTX-resistant tumors, with the majority involved of lipids and lipid-like molecules. Spearman’s correlation coefficient analysis indicated in vivo and ex vivo metabolic characteristics were highly consistent, exhibiting the highest positive correlation between in vivo GPC + PC and ex vivo GPC (r = 0.885, P < 0.001). These metabolic data suggested that abnormal choline concentrations were the results from the dysregulated glycerophospholipid metabolism, especially choline metabolism. The proteomics data indicated that the expressions of key enzymes glycerophosphocholine phosphodiesterase 1 (GPCPD1) and glycerophosphodiester phosphodiesterase 1 (GDE1) were significantly lower in the PTX-resistant tumors compared to the PTX-sensitive tumors (both P < 0.01). Decreased expressions of GPCPD1 and GDE1 in choline metabolism led to an increased GPC levels in the PTX-resistant EOCs, which was observed as an elevated total choline (tCho) on in vivo 1H-MRS.

Conclusions

These findings suggested that dysregulated choline metabolism was associated with PTX-resistance in EOCs and the elevated tCho on in vivo 1H-MRS could be as an indicator for the PTX-resistance in EOCs.
CD34+THY1+ synovial fibroblast subset in arthritic joints has high osteoblastic and chondrogenic potentials in vitro
Authors: Noda Seiji , Hosoya Tadashi , Komiya Yoji , Tagawa Yasuhiro , Endo Kentaro , Komori Keiichiro , Koga Hideyuki , Takahara Yasuhiro , Sugimoto Kazutaka , Sekiya Ichiro , Saito Tetsuya , Mizoguchi Fumitaka , Yasuda Shinsuke
Published: February 2022

Objective

Synovial fibroblasts (SFs) in rheumatoid arthritis (RA) and osteoarthritis (OA) play biphasic roles in joint destruction and regeneration of bone/cartilage as mesenchymal stem cells (MSCs). Although MSCs contribute to joint homeostasis, such function is impaired in arthritic joints. We have identified functionally distinct three SF subsets characterized by the expression of CD34 and THY1 as follows: CD34+THY1+, CD34−THY1−, and CD34−THY1+. The objective of this study was to clarify the differentiation potentials as MSCs in each SF subset since both molecules would be associated with the MSC function.

Methods

SF subsets were isolated from synovial tissues of 70 patients (RA: 18, OA: 52). Expressions of surface markers associated with MSCs (THY1, CD34, CD73, CD271, CD54, CD44, and CD29) were evaluated in fleshly isolated SF subsets by flow cytometry. The differentiation potentials of osteogenesis, chondrogenesis, and adipogenesis were evaluated with histological staining and a quantitative polymerase chain reaction of differentiation marker genes. Small interfering RNA was examined to deplete THY1 in SFs.

Results

The expression levels of THY1+, CD73+, and CD271+ were highest and those of CD54+ and CD29+ were lowest in CD34+THY1+ among three subsets. Comparing three subsets, the calcified area, alkaline phosphatase (ALP)-stained area, and cartilage matrix subset were the largest in the CD34+THY1+ subset. Consistently, the expressions of differentiation markers of the osteoblasts (RUNX2, ALPL, and OCN) or chondrocytes (ACAN) were the highest in the CD34+THY1+ subset, indicating that the CD34+THY1+ subset possessed the highest osteogenic and chondrogenic potential among three subsets, while the differentiation potentials to adipocytes were comparable among the subsets regarding lipid droplet formations and the expression of LPL and PPARγ. The knockdown of THY1 in bulk SFs resulted in impaired osteoblast differentiation indicating some functional aspects in this stem-cell marker.

Conclusion

The CD34+THY1+ SF subset has high osteogenic and chondrogenic potentials. The preferential enhancement of MSC functions in the CD34+THY1+ subset may provide a new treatment strategy for regenerating damaged bone/cartilage in arthritic joints.
Selection and validation of reference gene for RT-qPCR studies in co-culture system of mouse cementoblasts and periodontal ligament cells
Authors: Yong Jiawen , Groeger Sabine , Ruiz-Heiland Gisela , Ruf Sabine
Published: February 2022

Objective

RT-qPCR is a reliable method for gene expression analysis, but the accuracy of the quantitative data depends on the appropriate selection of reference genes. A Co-culture system consisting of periodontal ligament cells (SV-PDL) and cementoblasts (OCCM-30) to investigate the crosstalk between these two cell lines under orthodontic condition is essential for experimental orthodontic setups in-vitro. Therefore, we aimed to identify a set of reliable reference genes suitable for RT-qPCR studies for prospective co-culture systems of OCCM-30 and SV-PDL cells.

Results

The results demonstrated thatPPIB,GUSBandRPLP0turned out to be the three most stable reference genes for OCCM-30 in the co-culture system, whilePPIB,POLR2AandRPLP0have the three highest rankings for SV-PDL cells in the co-culture system. The most stable gene combination werePPIBandPOLR2Ain the co-culture system. In conclusion,PPIBis overall the most stably expressed reference gene for OCCM-30 or SV-PDL cell line in the system. The combination ofPPIBandPOLR2Aas reference genes are indicated to be the potential and mandatory to obtain accurate quantification results for normalizing RT-qPCR data in genes of interest expression in these two cell lines co-culture systems.
Hyperbaric oxygen treatment for long coronavirus disease-19: a case report
Authors: Bhaiyat Aisha M. , Sasson Efrat , Wang Zemer , Khairy Sherif , Ginzarly Mouzayan , Qureshi Umair , Fikree Moin , Efrati Shai
Published: February 2022

Background

The coronavirus disease 2019 pandemic has resulted in a growing population of individuals who experience a wide range of persistent symptoms referred to as “long COVID.” Symptoms include neurocognitive impairment and fatigue. Two potential mechanisms could be responsible for these long-term unremitting symptoms: hypercoagulability, which increases the risk of blood vessel occlusion, and an uncontrolled continuous inflammatory response. Currently, no known treatment is available for long COVID. One of the options to reverse hypoxia, reduce neuroinflammation, and induce neuroplasticity is hyperbaric oxygen therapy. In this article, we present the first case report of a previously healthy athletic individual who suffered from long COVID syndrome treated successfully with hyperbaric oxygen therapy.

Case presentation

A previously healthy 55-year-old Caucasian man presented 3 months after severe coronavirus disease 2019 infection with long COVID syndrome. His symptoms included a decline in memory, multitasking abilities, energy, breathing, and physical fitness. After evaluation that included brain perfusion magnetic resonance imaging, diffusion tensor imaging, computerized cognitive tests, and cardiopulmonary test, he was treated with hyperbaric oxygen therapy. Each session included exposure to 90 minutes of 100% oxygen at 2 atmosphere absolute pressure with 5-minute air breaks every 20 minutes for 60 sessions, 5 days per week. Evaluation after completing the treatment showed significant improvements in brain perfusion and microstructure by magnetic resonance imaging and significant improvement in memory with the most dominant effect being on nonverbal memory, executive functions, attention, information procession speed, cognitive flexibility, and multitasking. The improved cognitive functions correlated with the increased cerebral blood flow in brain regions as measured by perfusion magnetic resonance imaging. With regard to physical capacity, there was a 34% increase in the maximum rate of oxygen consumed during exercise and a 44% improvement in forced vital capacity. The improved physical measurements correlated with the regain of his pre-COVID physical capacity.

Conclusions

We report the first case of successfully treated long COVID symptoms with hyperbaric oxygen therapy with improvements in cognition and cardiopulmonary function. The beneficial effects of hyperbaric oxygen shed additional light on the pathophysiology of long COVID. As this is a single case report, further prospective randomized control studies are needed.
It probably worked: a Bayesian approach to evaluating the introduction of activity-based hospital payment in Israel
Authors: Waitzberg Ruth , Siegel Martin , Quentin Wilm , Busse Reinhard , Greenberg Dan
Published: February 2022

Background

In 2013–2014, Israel accelerated adoption of activity-based payments to hospitals. While the effects of such payments on patient length of stay (LoS) have been examined in several countries, there have been few analyses of incentive effects in the Israeli context of capped reimbursements and stretched resources.

Methods

We examined administrative data from the Israel Ministry of Health for 14 procedures from 2005 to 2016 in all not-for-profit hospitals (97% of the acute care beds). Survival analyses using a Weibull distribution allowed us to examine the non-negative and right-skewed data. We opted for a Bayesian approach to estimate relative change in LoS.

Results

LoS declined in 7 of 14 procedures analyzed, notably, in 6 out of 7 urological procedures. In these procedures, reduction in LoS ranged between 11% and 20%. The estimation results for the control variables are mixed and do not indicate a clear pattern of association with LoS.

Conclusions

The decrease in LoS freed resources to treat other patients, which may have resulted in reduced waiting times. It may have been more feasible to reduce LoS for urological procedures since these had relatively long LoS. Policymakers should pay attention to the effects of decreases in LoS on quality of care. Stretched hospital resources, capped reimbursements, retrospective subsidies and underpriced procedures may have limited hospitals' ability to reduce LoS for other procedures where no decrease occurred (e.g., general surgery).
Selfish personalities influencing start-up intention and motivation: a study of Vietnam
Authors: Lien Tran Thi Hong , Anh Tran Tu , Anh Truong Nhat , Anh Le Huu Tuan , Thao Ngo Thi Thien
Published: February 2022

This research explores the influences of selfish personalities of the Dark Triad on start-up intention and motives based on a sample of 400 university students in Vietnam, discovering mixed effects of narcissism, psychopathy, and Machiavellianism. A high level of narcissism and Machiavellianism leads to high start-up intention. There is a negative relationship of Machiavellianism with pro-social motive and a positive association with selfish entrepreneurship. In addition, narcissism is positively associated with pro-social start-up motives. This study has found no effect of psychopathy but a positive link to selfish entrepreneurial motivation. Implications have been suggested for educators and investors.
Good farm practices and improved processing technology of enset for sustainable hunger solution in Ethiopia
Authors: Kudama Gezahagn , Tolera Tadesse , Gebeyehu Lemane
Published: February 2022

Given the multi-benefits, enset cultivation has been continuously underutilized in Ethiopia. We assess best practices, processing technologies, environmental maintenance, multi-benefits of enset and its potency in hunger reduction in Ethiopia by reviewing evidence on good farm practices, improved technologies, sustainability, hunger reduction, inputs cost, and yields advantage of enset. The review results identify those best practices that optimize enset yield, technologies that facilitate extension services, processing and food qualities of enset. Moreover, we find that enset is a first-rated climate-smart crop, superior hunger solution because of its apparent capability to endure long periods (more than 5 years) of drought, highest yield, energy food supply, and costs advantages. In contrast, its long-period maturity, cultural perceptions, and little development policy attention given to enset limit its expansion. Therefore, exploring and creating universal access mechanism of early maturing and high-yielding varieties, processing technologies and mobile-based advices, involving best practices of enset in regular agricultural extension services, changing social perceptions optimize enset yield and production thereby it contributes environmental sustainability and cuts hunger challenges.
Major coagulation disorders and parameters in COVID-19 patients
Authors: Teimury Azadeh , Khameneh Mahshid Taheri , Khaledi Elahe Mahmoodi
Published: February 2022

Coronavirus disease 2019 (COVID-19), with a high prevalence rate, has rapidly infected millions of people around the world. Since viral infections can disrupt the coagulation and homeostasis cascades, various inflammatory and coagulation problems occur due to COVID-19 infection, similar to coronavirus epidemics in 2003 and 2004. According to multiple previous studies, in the present research, we reviewed the most commonly reported problems of COVID-19 patients, such as venous thromboembolism, pulmonary embolism, disseminated intravascular coagulation, etc. and investigated the causes in these patients. Coagulation and inflammatory markers, such as platelets and fibrinogen, C-reactive protein, lactate dehydrogenase, d-dimer, prothrombin time, etc., were also discussed, and the treatment options were briefly reviewed. In addition to coagulation treatments, regular examination of coagulation parameters and thrombotic complications can be helpful in the timely treatment of patients. Therefore, it is helpful to review the coagulation problems in COVID-19 patients. Although all mentioned problems and markers are important in COVID-19, some of them are more valuable in terms of diagnosis and prognosis.
Sparse laterally constrained inversion of surface-wave dispersion curves via minimum gradient support regularization
Authors: Guillemoteau Julien , Vignoli Giulio , Barreto Jeniffer , Sauvin Guillaume
Published: February 2022

We have developed a 1D laterally constrained inversion of surface-wave dispersion curves based on the minimum gradient support regularization, which allows solutions with tunable sharpness in the vertical and horizontal directions. The forward modeling consists of a finite-elements approach incorporated in a flexible nonparametric gradient-based inversion scheme, which has already demonstrated good stability and convergence capabilities when tested on other kinds of data. Our deterministic inversion procedure is performed in the shear-wave velocity log space as we noticed that the associated Jacobian indicates a reduced model dependency, and this, in turn, decreases the risks of local nonconvexity. We show several synthetics and one field example to demonstrate the effectiveness and the applicability of the proposed approach.
Separation and imaging of diffractions using a dilated convolutional neural network
Authors: Sheng Tongjie , Zhao Jingtao
Published: February 2022

Seismic diffractions provide high-resolution details of small-scale geologic discontinuities, and diffraction imaging can be an important contribution to the exploration of faults, fractures, and cavities. However, reflections with strong energy generally mask the existence of weak diffractions in seismic records, and separating diffractions is necessary to see the full benefit of diffraction imaging. Here, a modified convolutional neural network (CNN) is used for separating diffractions. The input wavefields are modeled as the summation of individual diffractions and reflections, the network parameters are learned from multiple input data instances by minimizing the distance between the output of the network and the diffractions, and reflections are implicitly removed. To enhance the diffraction separation performance, we have used dilated convolutions to aggregate diffraction information, then combined batch normalization and residual learning to speed up the training process. The modified CNN can realize adaptive diffraction separation and avoid setting parameters in the subsequent application process. The synthetic Sigsbee2A model demonstrates the performance of the proposed method in removing high-slope reflections and imaging small-scale scatterers. The application to the Nankai field data further illustrates the ability of the methods to extract weak diffractions beneath the interference of other waves, revealing potential reservoir-related geologic features.
Identification of sandstone-rich zones in upper bathyal, deep water environment on south Texas Gulf Coast
Authors: Ogiesoba Osareni C. , Zeng Hongliu
Published: February 2022

We document the results of a 3D seismic investigation undertaken in search of prospective hydrocarbon, sandstone-rich zones within the Eocene Yegua Formation, which is located in a shale-dominated environment in Jackson County, South Texas. Because of the preponderance of shale in this environment, diligent effort and methods were required to identify sandstone-rich zones. First, we used seismic sweetness and instantaneous frequency attributes to identify sandstone-rich zones. This procedure was then followed by a frequency-fusion method to validate results and estimate the thickness of predicted sandstone-rich intervals. Results show that these zones are characterized by low frequencies ranging from 0 to 15 Hz. We interpreted the depositional pattern to be slope channels and slope fans deposited in an upper bathyal environment, trapped by down-to-the-basin synthetic growth faults and shale ridges. The growth faults found within this Yegua deep water setting influence the sandstone-rich zones in two ways: (1) they act as a barrier against which sandstones are trapped and (2) they downfault sediments to deeper water, making recognizing the continuity of the channels difficult. On the basis of frequency fusion, we infer that the thickness of the sandstone-rich zones ranges from 30 to 45 m (100–150 ft). Although sweetness, frequency fusion, and instantaneous frequency attributes can help in identifying sandstone-rich zones in shale-dominated environments, a combination of these attributes and structure is required to determine whether the sandstone-rich zone could be a potential prospect.
Clozapine-induced gastrointestinal hypomotility: presenting features and outcomes, UK pharmacovigilance reports, 1992–2017
Authors: Handley S. A. , Every-Palmer S. , Ismail A. , Flanagan R. J.
Published: February 2022

Background

Clozapine-induced gastrointestinal hypomotility (CIGH) affects some 75% of patients treated with clozapine.

Aims

To document the incidence of potentially harmful CIGH in the UK.

Method

We studied spontaneous UK pharmacovigilance reports recorded as clozapine-related gastrointestinal adverse drug reactions, 1992–2017.

Results

There were 527 patients reported with potentially harmful CIGH; 33% (n = 172) died. Deaths averaged 1 per year 1992–1999, 5 per year 2000–2009 and 15 per year 2010–2017. Those who died were older (median 52 years v. 49 years) and had been prescribed clozapine for longer than those who recovered (median 11.3 years v. 4.8 years), but there was no difference in prescribed dose. Within the first 4 years of clozapine treatment, there were 169 reports of CIGH, of which 3% (n = 5) were fatal. At 10–14 years there were 63 reports of CIGH, of which 25% (n = 16) were fatal. Among the deaths, males were younger (median 51, range 22–89 v. median 57, range 24–89 years) with higher clozapine doses (median 450, range 100–900 v. median 300, range 12.5–800 mg/d) than females. In non-fatal CIGH, surgery was the most frequent outcome (n = 92). The procedures included appendectomy, ileostomy, total/partial colectomy, colostomy/stoma and proctosigmoidectomy. Clozapine dosage was reduced in 6 patients, stopped and restarted in 23, ‘continued’ in 6 and discontinued permanently in at least 76 patients.

Conclusions

The risk of serious morbidity/mortality from CIGH is substantial. The need to actively monitor bowel function and give laxatives to patients treated with clozapine is clear.
Artificial intelligence and suicide prevention: A systematic review
Authors: Lejeune Alban , Le Glaz Aziliz , Perron Pierre-Antoine , Sebti Johan , Baca-Garcia Enrique , Walter Michel , Lemey Christophe , Berrouiguet Sofian
Published: February 2022

Background

Suicide is one of the main preventable causes of death. Artificial intelligence (AI) could improve methods for assessing suicide risk. The objective of this review is to assess the potential of AI in identifying patients who are at risk of attempting suicide.

Methods

A systematic review of the literature was conducted on PubMed, EMBASE, and SCOPUS databases, using relevant keywords.

Results

Thanks to this research, 296 studies were identified. Seventeen studies, published between 2014 and 2020 and matching inclusion criteria, were selected as relevant. Included studies aimed at predicting individual suicide risk or identifying at-risk individuals in a specific population. The AI performance was overall good, although variable across different algorithms and application settings.

Conclusions

AI appears to have a high potential for identifying patients at risk of suicide. The precise use of these algorithms in clinical situations, as well as the ethical issues it raises, remain to be clarified.
Novel PTH Gene Mutations Causing Isolated Hypoparathyroidism
Authors: Hawkes Colin P , Al Jubeh Jamal M , Li Dong , Tucker Susan E , Rajiyah Tara , Levine Michael A
Published: February 2022

Context

Parathyroid hormone (PTH) gene mutations represent a rare cause of familial isolated hypoparathyroidism (FIH). These defects can cause hypoparathyroidism with increased or decreased serum levels of PTH through 1) impaired PTH synthesis; 2) induction of parathyroid cell apoptosis; or 3) secretion of bioinactive PTH molecules. Eight pathogenic mutations of this gene have been described previously.

Objective

Through describing 2 novel mutations of the PTH gene, we aim to extend the molecular basis for FIH and further refine the proposed mechanisms by which PTH mutations cause hypoparathyroidism.

Methods

Proband case reports were compiled with extended family analysis. The probands in both kindreds presented before age 10 days with hypocalcemia and elevated phosphate levels. Proband A had low PTH levels, whereas these levels were elevated in Proband B. Proband B was initially diagnosed with pseudohypoparathyroidism. Methylation analysis was performed of CpG dinucleotides within 3 GNAS differentially methylated regions; whole-genome sequencing; and PTH infusion with analysis of nephrogenous 3′,5′-cyclic adenosine 5′-monophosphate.

Results

Proband A had a novel heterozygous sequence change in exon 2 of the PTH gene, c.46_47delinsAA (p.Ala16Lys), and proband B had a novel homozygous nucleotide transition in PTH exon 3 (c.128G > A; p.G43E) that led to replacement of glycine by glutamic acid at position 12 of PTH 1-84. PTH 1-34 infusion demonstrated that renal responsiveness to PTH was intact and not antagonized by circulating bioinactive PTH.

Conclusion

PTH gene mutations are uncommon causes of hypoparathyroidism, but can be misdiagnosed as disorders of gland development or receptor function if PTH levels are decreased or elevated, respectively. Genetic testing should be considered early in the diagnostic approach to these presentations.
Theory to the Rescue of Large-Scale Models: Edmond Malinvaud's View on the Search for Microfoundations
Authors: Renault Matthieu
Published: February 2022

Edmond Malinvaud's case is peculiar in the history of macroeconomics as he committed to two different microfoundational programs, namely, the disequilibrium theory (more properly, the non-Walrasian approach) and the practice of large-scale macroeconomic modeling. Such a twofold commitment was far from anecdotal because Malinvaud regarded these programs as fully compatible. The search for microfoundations he promoted did not aim at reconsidering the autonomy of macroeconomics. It was instead subject to the condition of being connected and oriented toward the needs of large-scale models. The best illustration was Malinvaud's own contributions to the non-Walrasian approach throughout the 1970s and 1980s, by which he intended to rationalize and improve the practice of French large-scale modeling.