bluuebunny/crossref_metadata_2025 huggingface dataset:
Poplar aquaporin PIP1;1 promotes Arabidopsis growth and development
Authors: Leng Huani , Jiang Cheng , Song Xueqin , Lu Mengzhu , Wan Xianchong
Published: June 2021

Background

Root hydraulic conductance is primarily determined by the conductance of living tissues to radial water flow. Plasma membrane intrinsic proteins (PIPs) in root cortical cells are important for plants to take up water and are believed to be directly involved in cell growth.

Results

In this study, we found that constitutive overexpression of the poplar root-specific gene PtoPIP1;1 in Arabidopsis accelerated bolting and flowering. At the early stage of the developmental process, PtoPIP1;1 OE Arabidopsis exhibited faster cell growth in both leaves and roots. The turgor pressure of plants was correspondingly increased in PtoPIP1;1 OE Arabidopsis, and the water status was changed. At the same time, the expression levels of flowering-related genes (CRY1, CRY2 and FCA) and hub genes in the regulatory networks underlying floral timing (FT and SOC1) were significantly upregulated in OE plants, while the floral repressor FLC gene was significantly downregulated.

Conclusions

Taken together, the results of our study indicate that constitutive overexpression of PtoPIP1;1 in Arabidopsis accelerates bolting and flowering through faster cell growth in both the leaf and root at an early stage of the developmental process. The autonomous pathway of flowering regulation may be executed by monitoring developmental age. The increase in turgor and changes in water status with PtoPIP1;1 overexpression play a role in promoting cell growth.
Genome-wide association study and transcriptome analysis discover new genes for bacterial leaf blight resistance in rice (Oryza sativa L.)
Authors: Shu Xinyue , Wang Aijun , Jiang Bo , Jiang Yuqi , Xiang Xing , Yi Xiaoqun , Li Shuangcheng , Deng Qiming , Wang Shiquan , Zhu Jun , Liang Yueyang , Liu Huainian , Zou Ting , Wang Lingxia , Li Ping , Zheng Aiping
Published: June 2021

Background

Rice (Oryza sativa) bacterial leaf blight (BLB), caused by the hemibiotrophicXanthomonas oryzaepv.oryzae(Xoo), is one of the most devastating diseases affecting the production of rice worldwide. The development and use of resistant rice varieties or genes is currently the most effective strategy to control BLB.

Results

Here, we used 259 rice accessions, which are genotyped with 2 888 332 high-confidence single nucleotide polymorphisms (SNPs). Combining resistance variation data of 259 rice lines for twoXooraces observed in 2 years, we conducted a genome-wide association study (GWAS) to identify quantitative trait loci (QTL) conferring plant resistance against BLB. The expression levels of genes, which contains in GWAS results were also identified between the resistant and susceptible rice lines by transcriptome analysis at four time points after pathogen inoculation. From that 109 candidate resistance genes showing significant differential expression between resistant and susceptible rice lines were uncovered. Furthermore, the haplotype block structure analysis predicted 58 candidate genes for BLB resistance based on Chr. 7_707158 with a minimumP-value (–log 10P = 9.72). Among them, two NLR protein-encoding genes, LOC_Os07g02560 and LOC_Os07g02570, exhibited significantly high expression in the resistant line, but had low expression in the susceptible line of rice.

Conclusions

Together, our results reveal novel BLB resistance gene resources, and provide important genetic basis for BLB resistance breeding of rice crops.
Incorporating single-arm studies in meta-analysis of randomised controlled trials: a simulation study
Authors: Singh Janharpreet , Abrams Keith R. , Bujkiewicz Sylwia
Published: June 2021

Background

Use of real world data (RWD) from non-randomised studies (e.g. single-arm studies) is increasingly being explored to overcome issues associated with data from randomised controlled trials (RCTs). We aimed to compare methods for pairwise meta-analysis of RCTs and single-arm studies using aggregate data, via a simulation study and application to an illustrative example.

Methods

We considered contrast-based methods proposed by Begg & Pilote (1991) and arm-based methods by Zhang et al (2019). We performed a simulation study with scenarios varying (i) the proportion of RCTs and single-arm studies in the synthesis (ii) the magnitude of bias, and (iii) between-study heterogeneity. We also applied methods to data from a published health technology assessment (HTA), including three RCTs and 11 single-arm studies.

Results

Our simulation study showed that the hierarchical power and commensurate prior methods by Zhang et al provided a consistent reduction in uncertainty, whilst maintaining over-coverage and small error in scenarios where there was limited RCT data, bias and differences in between-study heterogeneity between the two sets of data. The contrast-based methods provided a reduction in uncertainty, but performed worse in terms of coverage and error, unless there was no marked difference in heterogeneity between the two sets of data.

Conclusions

The hierarchical power and commensurate prior methods provide the most robust approach to synthesising aggregate data from RCTs and single-arm studies, balancing the need to account for bias and differences in between-study heterogeneity, whilst reducing uncertainty in estimates. This work was restricted to considering a pairwise meta-analysis using aggregate data.
Validity of using mobile phone surveys to evaluate community health worker program in Mali
Authors: Chen Xiaomeng , Mohan Diwakar , Maïga Abdoulaye , Frost Emily , Coulibaly Djeneba , Basil Luay , Gueye Birahim Yaguemar , Guindo Mariam Traore , Keita Assa Sidibé , Keita Haoua Dembelé , Marx Melissa A.
Published: June 2021

Background

The monitoring and evaluation of public health programs based on traditional face-to-face interviews in hard-to-reach and unstable regions present many challenges. Mobile phone-based methods are considered to be an effective alternative, but the validity of mobile phone-based data for assessing implementation strength has not been sufficiently studied yet. Nested within an evaluation project for an integrated community case management (iCCM) and family planning program in Mali, this study aimed to assess the validity of a mobile phone-based health provider survey to measure the implementation strength of this program.

Methods

From July to August 2018, a cross-sectional survey was conducted among the community health workers (ASCs) from six rural districts working with the iCCM and family planning program. ASCs were first reached to complete the mobile phone-based survey; within a week, ASCs were visited in their communities to complete the in-person survey. Both surveys used identical implementation strength tools to collect data on program activities related to iCCM and family planning. Sensitivity and specificity were calculated for each implementation strength indicator collected from the phone-based survey, with the in-person survey as the gold standard. A threshold of ≥ 80% for sensitivity and specificity was considered adequate for evaluation purposes.

Results

Of the 157 ASCs interviewed by mobile phone, 115 (73.2%) were reached in person. Most of the training (2/2 indicators), supervision (2/3), treatment/modern contraceptive supply (9/9), and reporting (3/3) indicators reached the 80% threshold for sensitivity, while only one supervision indicator and one supply indicator reached 80% for specificity. In contrast, most of the stock-out indicators (8/9) reached 80% for specificity, while only two indicators reached the threshold for sensitivity.

Conclusions

The validity of mobile phone-based data was adequate for general training, supervision, and supply indicators for iCCM and family planning. With sufficient mobile phone coverage and reliable mobile network connection, mobile phone-based surveys are useful as an alternative for data collection to assess the implementation strength of general activities in hard-to-reach areas.
Recurrent epistaxis from inflamed granulated tissue and an associated pseudoaneurysm of the internal carotid artery: case report
Authors: Kim Ja Yoon , Kim Yong Bae , Chung Joonho
Published: June 2021

Background

Chronic inflamed tissue in nasal cavity is a rare complication of transsphenoidal approach (TSA). Inflamed tissue is rich in blood vessels, which can lead to frequent nosebleeds. In addition, chronic inflammation can cause pseudoaneurysm, whose rupture results in massive epistaxis. There have been few reported cases of pseudoaneurysm of ICA occurring more than 10 years after TSA surgery.

Case presentation

We report a case of a patient who had recurrent epistaxis for over a decade after TSA surgery, and analyzed the causes of the nosebleeds. The aspect of occurrence of the nosebleeds and the result of biopsy and imaging tests suggest that the nosebleeds were due to chronic inflamed tissue and an associated pseudoaneurysm. The rupture of pseudoaneurysm recurred after treatment with stent placement, and brain abscess was developed. After removing the inflamed tissue by endoscopic resection, the patient no longer had recurrence of ruptured pseudoaneurysm or nosebleeds.

Conclusions

In patients with recurrent nosebleeds, the possibility of intranasal inflammation and subsequent pseudoaneurysm should be considered. Therefore, people who consistently have epistaxis after TSA, even if the bleeding is not in large amount, should be actively screened and treated for nasal chronic inflammation.
Identification of women at risk for hereditary breast and ovarian cancer in a sample of 1000 Slovenian women: a comparison of guidelines
Authors: Kotnik Urska , Peterlin Borut , Lovrecic Luca
Published: June 2021

Background

An important number of breast and ovarian cancer cases is due to a strong genetic predisposition. The main tool for identifying individuals at risk is recognizing a suggestive family history of cancer. We present a prospective study on applying three selected clinical guidelines to a cohort of 1000 Slovenian women to determine the prevalence of at-risk women according to each of the guidelines and analyze the differences amongst the guidelines.

Methods

Personal and family history of cancer was collected for 1000 Slovenian women. Guidelines by three organizations: National Comprehensive Cancer Network (NCCN), American College of Medical Genetics in cooperation with National Society of Genetic Counselors (ACMG/NSGC), and Society of Gynecologic Oncology (SGO) were applied to the cohort. The number of women identified, the characteristics of the high-risk population, and the agreement between the guidelines were explored.

Results

NCCN guidelines identify 13.2% of women, ACMG/NSGC guidelines identify 7.1% of women, and SGO guidelines identify 7.0% of women from the Slovenian population, while 6.2% of women are identified by all three guidelines as having high-risk for hereditary breast and ovarian cancer.

Conclusions

We identified 13.7% of women from the Slovenian population as being at an increased risk for breast and ovarian cancer based on their personal and family history of cancer using all of the guidelines. There are important differences between the guidelines. NCCN guidelines are the most inclusive, identifying nearly twice the amount of women as high-risk for hereditary breast and ovarian cancer as compared to the AGMG/NSCG and SGO guidelines in the Slovenian population.
Differences in cause and 12-month follow-up outcome of parkinsonian symptoms in depressed older adults treated with antipsychotics: a case series
Authors: Politis Anastasios , Kokras Nikolaos , Souvatzoglou Michael , Siarkos Kostas , Toulas Panagiotis , Potagas Constantin , Hatzipanagiotou Theodoros , Limouris Georgios , Alexopoulos Panagiotis
Published: June 2021

Background

Parkinsonian symptoms are common adverse effects of antipsychotics. Older adults are particularly vulnerable to drug-induced parkinsonism. Nonetheless, parkinsonian symptoms in seniors treated with antipsychotics cannot be straightforwardly attributed to antipsychotic medication. A comprehensive diagnostic workup is necessary in many cases in order to shed light on the cause of such symptoms in this patient population.

Case series

Eight cases of hospitalized depressed older adults with parkinsonian symptoms, who were treated for at least one year with antipsychotics, are reported. Based on neurological consultation, structural brain imaging and Ioflupane (I-123) dopamine transporter (DAT) single photon emission computerized tomography (SPECT), Parkinson’s disease was diagnosed in one case, idiopathic tremor in another, vascular parkinsonism in another one, while in another individual parkinsonian symptoms persisted at 12-month post-discharge follow-up even though his/her symptoms were classified as drug-induced on discharge. In four patients, parkinsonian symptoms were definitely drug-induced and no movement disturbances were reported at follow-up.

Conclusions

Differences in the cause and outcome of parkinsonian symptoms in seniors treated with antipsychotics merit systematic and in-depth study considering the therapeutic and prognostic implications of an accurate detection of the cause of such symptoms. Familiarizing clinical psychiatrists with these differences could pave the way towards approaching seniors with severe, atypical and/or persistent parkinsonian symptoms in a more individualized diagnostic and therapeutic manner, and towards more cautious prescribing of antipsychotics in this age group.
Posttraumatic stress disorder correlates among internally displaced Yazidi population following Islamic state of Iraq and Syria attacks in Iraq
Authors: Taha Perjan Hashim , Taib Nezar Ismet , Sulaiman Hushyar Musa
Published: June 2021

Background

In 2014, the so-called Islamic State of Iraq and Syria (ISIS) took over one-third of Iraq. This study measured the rate of posttraumatic stress disorder (PTSD) among Iraqi Yazidi internally displaced persons (IDPs) and examined associated demographic and traumatic risk factors.

Methods

A cross-sectional survey was carried out in April–June 2015 at the Khanke camp, northern Iraq. Trauma exposure and PTSD were measured by the Harvard Trauma Questionnaire (Iraqi version).

Results

Of 814 adult Yazidi IDPs, 34% screened positive for PTSD. Avoidance and intrusion symptoms had the highest means (M = 3.16, SD = 0.86 and M = 2.63, SD = 0.59 respectively). Associated factors of PTSD included exposure to a high number of traumatic events, unmet basic needs and having witnessed the destruction of residential or religious areas (OR = 1.39, 95% CI: 1.02–1.9 and OR = 1.25, 95% CI: 1.01–1.53 respectively). Being a widow was the only linked demographic factor (OR = 15.39, 95% CI: 3.02–78.39).

Conclusions

High traumatic exposure, specifically unmet basic needs and having witnessed destruction, was an important predictor of PTSD among Yazidi IDPs. These findings are important for mental health planning for IDPs in camps.
No prescription? No problem: drivers of non-prescribed sale of antibiotics among community drug retail outlets in low and middle income countries: a systematic review of qualitative studies
Authors: Belachew Sewunet Admasu , Hall Lisa , Erku Daniel Asfaw , Selvey Linda A.
Published: June 2021

Background

Non-prescription dispensing of antibiotics, one of the main sources of antibiotic misuse or over use, is a global challenge with detrimental public health consequences including acceleration of the development of antimicrobial resistance, and is facilitated by various intrinsic and extrinsic drivers. The current review aimed to systematically summarise and synthesise the qualitative literature regarding drivers of non-prescribed sale of antibiotics among community drug retail outlets in low and middle income countries.

Methods

Four electronic databases (PubMed, CINAHL, Scopus and Google Scholar) and reference lists of the relevant articles were searched. The Joanna Briggs Institute’s Critical Appraisal Checklist for qualitative studies was used to assess the quality of included studies. The enhancing transparency in reporting the synthesis of qualitative research statement was used to guide reporting of results. Data were coded using NVivo 12 software and analysed using both inductive and deductive thematic analysis.

Results

A total of 23 articles underwent full text review and 12 of these met the inclusion criteria. Four main themes were identified in relation to facilitators of non-prescribed sale of antibiotics among community drug retail outlets: i) the business orientation of community drug retail outlets and tension between professionalism and commercialism; ii) customers’ demand pressure and expectation; iii); absence of or a lax enforcement of regulations; and iv) community drug retail outlet staff’s lack of knowledge and poor attitudes about antibiotics use and scope of practice regarding provision.

Conclusions

This review identified several potentially amendable reasons in relation to over the counter dispensing of antibiotics. To contain the rise of antibiotic misuse or over use by targeting the primary drivers, this review suggests the need for strict law enforcement or enacting new strong regulation to control antibiotic dispensing, continuous and overarching refresher training for community drug retail outlet staff about antibiotic stewardship, and holding public awareness campaigns regarding rational antibiotic use.
Anatomical sites (Takasaki’s segmentation) predicts the recurrence-free survival of hepatocellular carcinoma
Authors: Qin Wei , Wang Li , Hu Beiyuan , Tian Huan , Xiao Cuicui , Luo Huanxian , Yang Yang
Published: June 2021

Background

Until now, several classification staging system and treatment algorithm for hepatocelluar carcinoma (HCC) has been presented. However, anatomical location is not taken into account in these staging systems. The aim of this study is to investigate whether anatomical sites could predict the postoperative recurrence of HCC patients.

Methods

294 HCC patients were enrolled in this retrospective study. A novel score classification based on anatomical sites was established by a Cox regression model and validated in the internal validation cohort.

Results

HCC patients were stratified according to the novel score classification into three groups (score 0, score 1–3 and score 4–6). The predictive accuracy of the novel recurrence score for HCC patients as determined by the area under the receiver operating characteristic curves (AUCs) at 1, 3, and 5 years (AUCs 0.703, 0.706, and 0.605) was greater than that of the other representative classification systems. These findings were supported by the internal validation cohort. For patients with Barcelona Clinic Liver Cancer (BCLC) 0 and A stage, our data demonstrated that there was no significant difference in recurrence-free survival (RFS) between patients with score 0 and liver transplantation recipients. Additionally, we introduced this novel classification system to guide anatomical liver resection for centrally located liver tumors.

Conclusion

The novel score classification may provide a reliable and objective model to predict the RFS of HCC after hepatic resection.
Correction to: Sexual assault: women’s voices on the health impacts of not being believed by police
Authors: McQueen Karen , Murphy-Oikonen Jodie , Miller Ainsley , Chambers Lori
Published: June 2021

An amendment to this paper has been published and can be accessed via the original article.
SEPIA: simulation-based evaluation of prioritization algorithms
Authors: Almaraz Kimberly , Jang Tyler , Lewis McKenna , Ngo Titan , Song Miranda , Moshiri Niema
Published: June 2021

Background

The ability to prioritize people living with HIV (PLWH) by risk of future transmissions could aid public health officials in optimizing epidemiological intervention. While methods exist to perform such prioritization based on molecular data, their effectiveness and accuracy are poorly understood, and it is unclear how one can directly compare the accuracy of different methods. We introduce SEPIA (Simulation-based Evaluation of PrIoritization Algorithms), a novel simulation-based framework for determining the effectiveness of prioritization algorithms. SEPIA expands upon prior related work by defining novel metrics of effectiveness with which to compare prioritization techniques, as well as by creating a simulation-based tool with which to perform such effectiveness comparisons. Under several metrics of effectiveness that we propose, we compare two existing prioritization approaches: one phylogenetic (ProACT) and one distance-based (growth of HIV-TRACE transmission clusters).

Results

Using all proposed metrics, ProACT consistently slightly outperformed the transmission cluster growth approach. However, both methods consistently performed just marginally better than random, suggesting that there is significant room for improvement in prioritization tools.

Conclusion

We hope that, by providing ways to quantify the effectiveness of prioritization methods in simulation, SEPIA will aid researchers in developing novel risk prioritization tools for PLWH.
Long-term safety evaluation of Daxocox® tablets (enflicoxib) in dogs after weekly oral administrations for seven months
Authors: Homedes Josep , Salichs Marta , Guzman Antonio
Published: June 2021

Background

Daxocox® [Ecuphar/Animalcare Group] contains the selective COX-2 inhibitor enflicoxib, approved in the EU for the treatment of pain and inflammation associated with osteoarthritis in dogs. The safety of Daxocox® was evaluated in a target animal safety study: Groups of 4 dogs per sex each were treated once weekly with placebo or Daxocox tablets at 1-, 3- and 5-times (1X, 3X and 5X) the maximum recommended therapeutic dose of enflicoxib (0, 4, 12 or 20 mg/kg, respectively). After an initial loading dose, dogs in the placebo control, 1X and 3X groups were administered for 32 weeks, and those in the 5X group were administered for 13 weeks. Dogs were subjected to daily food consumption measurements and clinical and dose observations. Body weight measurements, physical examinations, clinical pathology, urinalysis, faecal occult blood (FOB) and electrocardiographic (ECG) and blood pressure measurements, buccal mucosal bleeding time (BMBT), ophthalmology and gastroduodenal endoscopy examinations were conducted throughout the study. At study completion, all dogs were subjected to gross necropsy. Histopathology was performed on selected tissues from all animals in all groups.

Results

No clinical signs were noted, and no toxicologically relevant dose-associated effects were observed.

Conclusions

Results show that Daxocox® is well-tolerated and has a broad safety margin when administered as directed in dogs.
Molecular analysis of the AGXT gene in Syrian patients suspected with primary hyperoxaluria type 1
Authors: Murad Hossam , Alhalabi Mohamad Baseel , Dabboul Amir , Alfakseh Nour , Nweder Mohamad Sayah , Zghib Youssef , Wannous Hala
Published: June 2021

Background

Characterization of the molecular basis of primary hyperoxaluria type 1 (PH-1) in Syria has been accomplished through the analysis of 90 unrelated chromosomes from 45 Syrians patients with PH-1 from different regions.

Methods

Alanine glyoxylate aminotransferase (AGXT) gene mutations have been analyzed by using molecular detection methods based on the direct DNA sequencing for all exons of the AGXT gene.

Results

Seventeen pathogenic mutations were detected in our patients. Six mutations were novels. The three most frequent mutations were c.33_34insC (p.Lys12fs) in Exon 1, c.584 T < G; p.Met195Arg in exon 5 and c.1007 T > A (p.Val336Asp) in exon 10, with a frequency of 33.3%, 12.2%, and 11.1%, respectively.

Conclusion

DNA sequencing used in this study can offer a useful method to investigate the mutations in Syrian PH-1 patients, and could offer an accurate tool for prenatal diagnosis and genetic counseling.
Superior production of heavy pamamycin derivatives using a bkdR deletion mutant of Streptomyces albus J1074/R2
Authors: Gläser Lars , Kuhl Martin , Stegmüller Julian , Rückert Christian , Myronovskyi Maksym , Kalinowski Jörn , Luzhetskyy Andriy , Wittmann Christoph
Published: June 2021

Background

Pamamycins are macrodiolides of polyketide origin which form a family of differently large homologues with molecular weights between 579 and 663. They offer promising biological activity against pathogenic fungi and gram-positive bacteria. Admittedly, production titers are very low, and pamamycins are typically formed as crude mixture of mainly smaller derivatives, leaving larger derivatives rather unexplored so far. Therefore, strategies that enable a more efficient production of pamamycins and provide increased fractions of the rare large derivatives are highly desired. Here we took a systems biology approach, integrating transcription profiling by RNA sequencing and intracellular metabolite analysis, to enhance pamamycin production in the heterologous host S. albus J1074/R2.

Results

Supplemented with l-valine, the recombinant producer S. albus J1074/R2 achieved a threefold increased pamamycin titer of 3.5 mg L−1 and elevated fractions of larger derivatives: Pam 649 was strongly increased, and Pam 663 was newly formed. These beneficial effects were driven by increased availability of intracellular CoA thioesters, the building blocks for the polyketide, resulting from l-valine catabolism. Unfavorably, l-valine impaired growth of the strain, repressed genes of mannitol uptake and glycolysis, and suppressed pamamycin formation, despite the biosynthetic gene cluster was transcriptionally activated, restricting production to the post l-valine phase. A deletion mutant of the transcriptional regulator bkdR, controlling a branched-chain amino acid dehydrogenase complex, revealed decoupled pamamycin biosynthesis. The regulator mutant accumulated the polyketide independent of the nutrient status. Supplemented with l-valine, the novel strain enabled the biosynthesis of pamamycin mixtures with up to 55% of the heavy derivatives Pam 635, Pam 649, and Pam 663: almost 20-fold more than the wild type.

Conclusions

Our findings open the door to provide rare heavy pamamycins at markedly increased efficiency and facilitate studies to assess their specific biological activities and explore this important polyketide further.
Combination therapy of zinc and trimethoprim inhibits infection of influenza A virus in chick embryo
Authors: El Habbal Magdi H.
Published: June 2021

Background

Respiratory RNA viruses including influenza virus have been a cause of health and economic hardships. These viruses depend on its host for replication and infection. Influenza virus infection is lethal to the chick embryo. We examined whether a combination of trimethoprim and zinc (Tri-Z), that acts on the host, can reduce the lethal effect of influenza A virus in chick embryo model.

Method

Influenza virus was isolated from patients and propagated in eggs. We determined viral load that infects 50% of eggs (50% egg lethal dose, ELD50). We introduced 10 ELD50into embryonated eggs and repeated the experiments using 100 ELD50. A mixture of zinc oxide (Zn) and trimethoprim (TMP) (weight/weight ratios ranged from 0.01 to 0.3, Zn/TMP with increment of 0.1) was tested for embryo survival of the infection (n = 12 per ratio, in triplicates). Embryo survival was determined by candling eggs daily for 7 days. Controls of Zn, TMP, saline or convalescent serum were conducted in parallel. The effect of Tri-Z on virus binding to its cell surface receptor was evaluated in a hemagglutination inhibition (HAI) assay using chicken red cells. Tri-Z was prepared to concentration of 10 mg TMP and 1.8 mg Zn per ml, then serial dilutions were made. HAI effect was expressed as scores where ++++ = no effect; 0 = complete HAI effect.

Results

TMP, Zn or saline separately had no effect on embryo survival, none of the embryos survived influenza virus infection. All embryos treated with convalescent serum survived. Tri-Z, at ratio range of 0.15–0.2 (optimal ratio of 0.18) Zn/TMP, enabled embryos to survive influenza virus despite increasing viral load (> 80% survival at optimal ratio). At concentration of 15 µg/ml of optimal ratio, Tri-Z had total HAI effect (scored 0). However, at clinical concentration of 5 µg/ml, Tri-Z had partial HAI effect (+ +).

Conclusion

Acting on host cells, Tri-Z at optimal ratio can reduce the lethal effect of influenza A virus in chick embryo. Tri-Z has HAI effect. These findings suggest that combination of trimethoprim and zinc at optimal ratio can be provided as treatment for influenza and possibly other respiratory RNA viruses infection in man.
Epidemiology and burden of progressive familial intrahepatic cholestasis: a systematic review
Authors: Jones-Hughes Tracey , Campbell Jo , Crathorne Louise
Published: June 2021

Background

Progressive familial intrahepatic cholestasis is a rare, heterogeneous group of liver disorders of autosomal recessive inheritance, characterised by an early onset of cholestasis with pruritus and malabsorption, which rapidly progresses, eventually culminating in liver failure. For children and their parents, PFIC is an extremely distressing disease. Significant pruritus can lead to severe cutaneous mutilation and may affect many activities of daily living through loss of sleep, irritability, poor attention, and impaired school performance.

Methods

Databases including MEDLINE and Embase were searched for publications on PFIC prevalence, incidence or natural history, and the economic burden or health-related quality of life of patients with PFIC. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.

Results

Three systematic reviews and twenty-two studies were eligible for inclusion for the epidemiology of PFIC including a total of 2603 patients. Study periods ranged from 3 to 33 years. Local population prevalence of PFIC was reported in three studies, ranging from 9.0 to 12.0% of children admitted with cholestasis, acute liver failure, or splenomegaly. The most detailed data come from the NAPPED study where native liver survival of >15 years is predicted in PFIC2 patients with a serum bile  acid concentration below 102 µmol/L following bile diversion surgery. Burden of disease was mainly reported through health-related quality of life (HRQL), rates of surgery and survival. Rates of biliary diversion and liver transplant varied widely depending on study period, sample size and PFIC type, with many patients have multiple surgeries and progressing to liver transplant. This renders data unsuitable for comparison.

Conclusion

Using robust and transparent methods, this systematic review summarises our current knowledge of PFIC. The epidemiological overview is highly mixed and dependent on presentation and PFIC subtype. Only two studies reported HRQL and mortality results were variable across different subtypes. Lack of data and extensive heterogeneity severely limit understanding across this disease area, particularly variation around and within subtypes.
N6-methyladenosine RNA modification regulates strawberry fruit ripening in an ABA-dependent manner
Authors: Zhou Leilei , Tang Renkun , Li Xiaojing , Tian Shiping , Li Bingbing , Qin Guozheng
Published: June 2021

Background

Epigenetic mark such as DNA methylation plays pivotal roles in regulating ripening of both climacteric and non-climacteric fruits. However, it remains unclear whether mRNA m6A methylation, which has been shown to regulate ripening of the tomato, a typical climacteric fruit, is functionally conserved for ripening control among different types of fruits.

Results

Here we show that m6A methylation displays a dramatic change at ripening onset of strawberry, a classical non-climacteric fruit. The m6A modification in coding sequence (CDS) regions appears to be ripening-specific and tends to stabilize the mRNAs, whereas m6A around the stop codons and within the 3′ untranslated regions is generally negatively correlated with the abundance of associated mRNAs. We identified thousands of transcripts with m6A hypermethylation in the CDS regions, including those ofNCED5,ABAR, andAREB1in the abscisic acid (ABA) biosynthesis and signaling pathway. We demonstrate that the methyltransferases MTA and MTB are indispensable for normal ripening of strawberry fruit, and MTA-mediated m6A modification promotes mRNA stability ofNCED5andAREB1, while facilitating translation ofABAR.

Conclusion

Our findings uncover that m6A methylation regulates ripening of the non-climacteric strawberry fruit by targeting the ABA pathway, which is distinct from that in the climacteric tomato fruit.
Genomic and transcriptomic analysis of the thermophilic lignocellulose-degrading fungus Thielavia terrestris LPH172
Authors: Tõlgo Monika , Hüttner Silvia , Rugbjerg Peter , Thuy Nguyen Thanh , Thanh Vu Nguyen , Larsbrink Johan , Olsson Lisbeth
Published: June 2021

Background

Biomass-degrading enzymes with improved activity and stability can increase substrate saccharification and make biorefineries economically feasible. Filamentous fungi are a rich source of carbohydrate-active enzymes (CAZymes) for biomass degradation. The newly isolated LPH172 strain of the thermophilic AscomyceteThielavia terrestrishas been shown to possess high xylanase and cellulase activities and tolerate low pH and high temperatures. Here, we aimed to illuminate the lignocellulose-degrading machinery and novel carbohydrate-active enzymes in LPH172 in detail.

Results

We sequenced and analyzed the 36.6-Mb genome and transcriptome of LPH172 during growth on glucose, cellulose, rice straw, and beechwood xylan. 10,128 predicted genes were found in total, which included 411 CAZy domains. Compared to other fungi, auxiliary activity (AA) domains were particularly enriched. A higher GC content was found in coding sequences compared to the overall genome, as well as a high GC3 content, which is hypothesized to contribute to thermophilicity. Primarily auxiliary activity (AA) family 9 lytic polysaccharide monooxygenase (LPMO) and glycoside hydrolase (GH) family 7 glucanase encoding genes were upregulated when LPH172 was cultivated on cellulosic substrates. Conventional hemicellulose encoding genes (GH10, GH11 and various CEs), as well as AA9 LPMOs, were upregulated when LPH172 was cultivated on xylan. The observed co-expression and co-upregulation of genes encoding AA9 LPMOs, other AA CAZymes, and (hemi)cellulases point to a complex and nuanced degradation strategy.

Conclusions

Our analysis of the genome and transcriptome ofT. terrestrisLPH172 elucidates the enzyme arsenal that the fungus uses to degrade lignocellulosic substrates. The study provides the basis for future characterization of potential new enzymes for industrial biomass saccharification.
lncRNA028466 regulates Th1/Th2 cytokine expression and associates with Echinococcus granulosus antigen P29 immunity
Authors: Wang Chan , Yang Song-Hao , Niu Nan , Tao Jia , Du Xian-Cai , Yang Ji-Hui , Zhu Ming-Xing , Wang Ya-Na , Zhao Wei
Published: June 2021

Background

Cystic echinococcosis (CE) is a parasitic disease that is caused byEchinococcus granulosus(Eg).The recombinantEchinococcus granulosusantigen P29 (rEg.P29) was shown to confer effective immunity to sheep and mice duringE. granulosussecondary infection in our previous study. In this study, we sought to investigate the ability of long noncoding RNA 028466 (lncRNA028466) as a regulator for the protective immunity mediated by rEg.P29 vaccination and to study the effects of lncRNA028466 on CD4+T cell differentiation in mice spleen.

Methods

Female BALB/c mice were divided into two groups and were vaccinated subcutaneously with rEg.P29 antigen and PBS as a control (12 mice each group). Following prime-boost vaccination, CD4+T, CD8+T, and B cells from the spleen were isolated by flow cytometry. Quantitative real-time PCR (qRT-PCR) was performed to measure the expression of lncRNA028466 in these three kinds of cells. Then, lncRNA028466 was overexpressed and knocked down in naive CD4+T cells, and Th1 and Th2 cytokine expression was detected. qRT-PCR, western blot, and ELISA were performed to evaluate the production of IFN-γ, IL-2, IL-4, and IL-10, and flow cytometry was performed to detect the differentiation of Th1 and Th2 subgroups.

Results

lncRNA028466 was significantly decreased after the second week of immunization with rEg.P29 antigen. The proportion of CD4+T cells was increased after rEg.P29 immunization. Overexpression of lncRNA028466 facilitated the production of IL-4, IL-10 and suppressed the production of IFN-γ, IL-2. Furthermore, after transfection with siRNA028466, IL-2 production was facilitated and IL-10 production was suppressed in naive CD4+T cells.

Conclusions

Immunization with rEg.P29 downregulated the expression of lncRNA028466, which was related to a higher Th1 immune response and a lower Th2 immune response. Our results suggest that lncRNA028466 may be involved in rEg.P29-mediated immune response by regulating cytokine expression of Th1 and Th2.
Host–multiparasite interactions in amphibians: a review
Authors: Herczeg Dávid , Ujszegi János , Kásler Andrea , Holly Dóra , Hettyey Attila
Published: June 2021

Parasites, including viruses, bacteria, fungi, protists, helminths, and arthropods, are ubiquitous in the animal kingdom. Consequently, hosts are frequently infected with more than one parasite species simultaneously. The assessment of such co-infections is of fundamental importance for disease ecology, but relevant studies involving non-domesticated animals have remained scarce. Many amphibians are in decline, and they generally have a highly diverse parasitic fauna. Here we review the literature reporting on field surveys, veterinary case studies, and laboratory experiments on co-infections in amphibians, and we summarize what is known about within-host interactions among parasites, which environmental and intrinsic factors influence the outcomes of these interactions, and what effects co-infections have on hosts. The available literature is piecemeal, and patterns are highly diverse, so that identifying general trends that would fit most host–multiparasite systems in amphibians is difficult. Several examples of additive, antagonistic, neutral, and synergistic effects among different parasites are known, but whether members of some higher taxa usually outcompete and override the effects of others remains unclear. The arrival order of different parasites and the time lag between exposures appear in many cases to fundamentally shape competition and disease progression. The first parasite to arrive can gain a marked reproductive advantage or induce cross-reaction immunity, but by disrupting the skin and associated defences (i.e., skin secretions, skin microbiome) and by immunosuppression, it can also pave the way for subsequent infections. Although there are exceptions, detrimental effects to the host are generally aggravated with increasing numbers of co-infecting parasite species. Finally, because amphibians are ectothermic animals, temperature appears to be the most critical environmental factor that affects co-infections, partly via its influence on amphibian immune function, partly due to its direct effect on the survival and growth of parasites. Besides their importance for our understanding of ecological patterns and processes, detailed knowledge about co-infections is also crucial for the design and implementation of effective wildlife disease management, so that studies concentrating on the identified gaps in our understanding represent rewarding research avenues.

Graphical Abstract
The heterogeneous human memory CCR6+ T helper-17 populations differ in T-bet and cytokine expression but all activate synovial fibroblasts in an IFNγ-independent manner
Authors: Dankers Wendy , den Braanker Hannah , Paulissen Sandra M. J. , van Hamburg Jan Piet , Davelaar Nadine , Colin Edgar M. , Lubberts Erik
Published: June 2021

Background

Chronic synovial inflammation is an important hallmark of inflammatory arthritis, but the cells and mechanisms involved are incompletely understood. Previously, we have shown that CCR6+ memory T-helper (memTh) cells and synovial fibroblasts (SF) activate each other in a pro-inflammatory feedforward loop, which potentially drives persistent synovial inflammation in inflammatory arthritis. However, the CCR6+ memTh cells are a heterogeneous population, containing Th17/Th22 and Th17.1 cells. Currently, it is unclear which of these subpopulations drive SF activation and how they should be targeted. In this study, we examined the individual contribution of these CCR6+ memTh subpopulations to SF activation and examined ways to regulate their function.

Methods

Th17/Th22 (CXCR3−CCR4+), Th17.1 (CXCR3+CCR4−), DP (CXCR3+CCR4+), and DN (CXCR3−CCR4−) CCR6+ memTh, cells sorted from PBMC of healthy donors or treatment-naïve early rheumatoid arthritis (RA) patients, were cocultured with SF from RA patients with or without anti-IL17A, anti-IFNγ, or 1,25(OH)2D3. Cultures were analyzed by RT-PCR, ELISA, or flow cytometry.

Results

Th17/Th22, Th17.1, DP, and DN cells equally express RORC but differ in production of TBX21 and cytokines like IL-17A and IFNγ. Despite these differences, all the individual CCR6+ memTh subpopulations, both from healthy individuals and RA patients, were more potent in activating SF than the classical Th1 cells. SF activation was partially inhibited by blocking IL-17A, but not by inhibiting IFNγ or TBX21. However, active vitamin D inhibited the pathogenicity of all subpopulations leading to suppression of SF activation.

Conclusions

Human CCR6+ memTh cells contain several subpopulations that equally express RORC but differ in TBX21, IFNγ, and IL-17A expression. All individual Th17 subpopulations are more potent in activating SF than classical Th1 cells in an IFNγ-independent manner. Furthermore, our data suggest that IL-17A is not dominant in this T cell-SF activation loop but that a multiple T cell cytokine inhibitor, such as 1,25(OH)2D3, is able to suppress CCR6+ memTh subpopulation-driven SF activation.
Tumour necrosis factor inhibitors reduce aortic stiffness progression in patients with long-standing rheumatoid arthritis
Authors: Giollo Alessandro , Cioffi Giovanni , Ognibeni Federica , Orsolini Giovanni , Dalbeni Andrea , Bixio Riccardo , Adami Giovanni , Fassio Angelo , Idolazzi Luca , Gatti Davide , Rossini Maurizio , Viapiana Ombretta
Published: June 2021

Background

Aortic stiffness index (AoSI) has to be considered a proxy outcome measure in patients with rheumatoid arthritis (RA). The aim of this study was to comparatively describe AoSI progression in two groups of RA patients on long-term treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) with or without tumour necrosis factor inhibitors (TNFi).

Methods

AoSI was evaluated by Doppler echocardiography at the level of the aortic root, using a two-dimensional guided M-mode evaluation. Eligible participants were assessed at baseline and after 12 months. Changes in serum lipids, glucose and arterial blood pressure were assessed. All patients who did not change DMARD treatment during follow-up were consecutively selected for this study.

Results

We included 107 (64 TNFi and 43 csDMARDs) RA patients. Most patients (74%) were in remission or low disease activity and had some CVD risk factors (45.8% hypertension, 59.8% dyslipidaemia, 45.3% smoking). The two groups did not differ significantly for baseline AoSI (5.95±3.73% vs 6.08±4.20%, p=0.867). Follow-up AoSI was significantly increased from baseline in the csDMARDs group (+1.00%; p<0.0001) but not in the TNFi group (+0.15%, p=0.477). Patients on TNFi had significantly lower follow-up AoSI from baseline than the csDMARDs group (−1.02%, p<0.001; ANCOVA corrected for baseline AoSI, age and systolic blood pressure). Furthermore, follow-up AoSI was significantly lower in TNFi than in csDMARDs users with an increasing number of CVD risk factors.

Conclusion

Long-term treatment with TNFi was associated with reduced aortic stiffness progression in patients with established RA and several CVD risk factors.
Positive psychology interventions in in-patients with depression: influences of comorbidity and subjective evaluation of the training programme
Authors: Stemmler Antje , Staehle Regina , Heinemann Tina , Bender Matthias , Hennig Juergen
Published: June 2021

Background

Studies on positive psychology interventions (PPIs) have frequently demonstrated benefits for healthy participants and patients. However, effect sizes are moderate, and underlying inter-individual differences in responses were rarely investigated.

Aims

We investigated whether severity of depression and subjective evaluation of PPIs are relevant sources of variance in this respect.

Method

A 4-week group PPI programme (one 45-min session per week) was offered to 38 in-patients with depression. The control group (n = 38) was carefully matched and received treatment as usual. In the PPI group, emotional states were recorded before and after each session (responsiveness). Beck Depression Inventory-II scores at hospital admission and discharge were used to evaluate clinical effectiveness. The number of comorbidities (as an indicator of severity of disease) and patients’ evaluations of the PPI sessions were used as additional independent factors for overall treatment outcome.

Results

The PPI induced a highly significant improvement in positive emotional state and decrease in negative emotional state, indicating responsiveness. Moreover, positive affectivity increased from week to week only in patients with a low number of comorbidities (indicating effectiveness). With respect to overall treatment outcome (Beck Depression Inventory-II scores), positive attitude toward the PPI resulted in the largest improvement.

Conclusions

The results partly explain the variance in the effectiveness of PPIs. Moreover, they support the idea of personalised psychotherapy, and may inform discussion on whether patients with depression should be included in PPIs. However, additional individual characteristics should increase knowledge about individual predictors for effectiveness.
Polyvinyl Alcohol/Chitosan Single-Layered and Polyvinyl Alcohol/Chitosan/Eudragit RL100 Multi-layered Electrospun Nanofibers as an Ocular Matrix for the Controlled Release of Ofloxacin: an In Vitro and In Vivo Evaluation
Authors: Mirzaeei Shahla , Taghe Shiva , Asare-Addo Kofi , Nokhodchi Ali
Published: June 2021

A novel nanofiber insert was prepared with a modified electrospinning method to enhance the ocular residence time of ofloxacin (OFX) and to provide a sustained release pattern by covering hydrophilic polymers, chitosan/polyvinyl alcohol (CS/PVA) nanofibers, with a hydrophobic polymer, Eudragit RL100 in layers, and by glutaraldehyde (GA) cross-linking of CS-PVA nanofibers for the treatment of infectious conjunctivitis. The morphology of the prepared nanofibers was studied using scanning electron microscopy (SEM). The average fiber diameter was found to be 123 ± 23 nm for the single electrospun nanofiber with no cross-linking (OFX-O). The single nanofibers, cross-linked for 10 h with GA (OFX-OG), had an average fiber diameter of 159 ± 30 nm. The amount of OFX released from the nanofibers was measured in vitro and in vivo using UV spectroscopy and microbial assay methods against Staphylococcus aureus, respectively. The antimicrobial efficiency of OFX formulated in cross-linked and non-cross-linked nanofibers was affirmed by observing the inhibition zones of Staphylococcus aureus and Escherichia coli. In vivo studies using the OFX nanofibrous inserts on a rabbit eye confirmed a sustained release pattern for up to 96 h. It was found that the cross-linking of the nanofibers by GA vapor could reduce the burst release of OFX from OFX-loaded CS/PVA in one layer and multi-layered nanofibers. In vivo results showed that the AUC0–96 for the nanofibers was 9–20-folds higher compared to the OFX solution. This study thus demonstrates the potential of the nanofiber technology is being utilized to sustained drug release in ocular drug delivery systems.