bluuebunny/crossref_metadata_2025 huggingface dataset:
Perceptions of Climate Risk and Use of Climate Risk Information by Natural Resource Conservation Stakeholders Participating in ADVANCE Projects in Asia and Latin America
Authors: De Mel Manishka , Solecki William , Horton Radley , Bartlett Ryan , Hehmeyer Abigail , Martin Shaun , Rosenzweig Cynthia
Published: March 2021

Integrating climate risk information into resilience-building activities in the field is important to ensure that adaptation is based on the best available science. Despite this, many challenges exist when developing, communicating, and incorporating climate risk information. There are limited resources on how stakeholders perceive risks, use risk information, and what barriers exist to limit knowledge integration. This paper seeks to define the following: 1) What do conservation stakeholders consider to be the most significant climate risks they face now and possibly in the future? 2) What have been the most significant barriers to their using climate risk information? 3) What sources and types of knowledge would be most useful for these managers to overcome these barriers? A survey was conducted among stakeholders (n = 224) associated with World Wildlife Fund projects in tropical and subtropical countries. A very high proportion of stakeholders used climate risk information and yet faced integration-related challenges, which included too much uncertainty and the lack of a relevant scale for planning. The main factors preventing the use of climate risk information in decision-making were unavailability of climate risk information, no or limited financial or human resources available to respond, lack of organizational mandate or support, and no or limited institutional incentives. Comparing perceived current and future risks revealed a decline in concern for some future climate hazards. Survey respondents identified scientific reports, climate scientists, and online sources as the most useful information sources of climate risk information, while (i) maps and illustrations; (ii) scenarios format; and (iii) data tables, graphs, and charts were identified as user-friendly formats.
Chronic Invasive Fungal Sinusitis With Negative Histopathology: A Diagnostic Challenge
Authors: Ning Anne , Kocharyan Arminé , Brown W Colby , D’Anza Brian
Published: March 2021

Although the diagnosis of chronic invasive fungal sinusitis relies chiefly on identification of invasive fungi on histology, the insidious nature of the disease can preclude detection of fungal organisms. Here, we present a case of chronic invasive fungal sinusitis with negative histopathologic findings and a definitive diagnosis made through fungal DNA detection. Clinicians should consider polymerase chain reaction an important complement to histology and culture in the diagnosis of chronic invasive fungal sinusitis.
A Pilot Investigation of the Pediatric Nasal Microbiome
Authors: Mahajan Elish , Cheng Jeffrey
Published: March 2021

This proof‐of‐concept study demonstrates that sinonasal microbiome sequencing with suctioned nasal secretions in children is technically feasible. Eighteen children were enrolled: 11 with symptoms of rhinosinusitis and 7 controls. Samples were collected via a sterile flexible respiratory suction catheter into a suction trap. Samples were analyzed with 16S ribosomal RNA sequencing and subsequent phylogenic mapping. The log2‐fold differential abundance in class demonstrated significantly higher quantities of bacteria from the classes Negativicutes, Bacilli, Mollicutes, and Alphaproteobacteria as compared with controls, with a false discovery rate–corrected P value <.01 for all 4. The experimental group showed a higher range of alpha diversity than the control group, although none of the measures of alpha diversity showed a statistically significant difference. Overall our study demonstrates that sinonasal microbiome sequencing with suctioned nasal secretions is a readily available and technically feasible alternative for study of the pediatric sinonasal microbiome.
Correlation between testicular volume and histological findings in children with unilateral cryptorchidism: Potential impact on future fertility
Authors: Spinelli Claudio , Morelli Girolamo , Cito Gianmartin , Bertocchini Alessia , Ghionzoli Marco , Pucci Angela , Cocci Andrea , Morganti Riccardo , Strambi Silvia
Published: March 2021

Objectives:

Our aim is to assess the correlation between testicular volume and histological findings in children with unilateral cryptorchidism.

Methods:

From September 2016 to August 2018, from 60 patients surgically treated for cryptorchidism, 45 children were enrolled in this single-center prospective study. Depending on the degree of testicular volume reduction, patients were divided into Group 1 with <20% reduction and Group 2 with reduction ⩾20%. Patients underwent unilateral orchidopexy and simultaneous biopsy of the undescended testis. Tanner stage was assigned. Tubular Fertility Index was measured.

Results:

Group 1 included 20 patients (44.4%) and Group 2 included 25 patients (55.5%). Mean age was 2.10 years (range 12 months–3.8 years) in Group 1 and 2.8 years (range 18 months–4.41 years) in Group 2. Although there is a positive correlation between testicular volume and Tubular Fertility Index, no significant association was found between groups ( p-value = 0.29). Furthermore, histological patterns did not differ significantly among groups.

Conclusions:

The degree of volume reduction in undescended testis does not seem to correlate significantly with the severity of histological changes that accompany cryptorchidism. Tubular Fertility Index could serve as objective tool for the assessment of future fertility.
Study on the influence of linear and nonlinear distribution of crosswind on the motion of aircraft wake vortex
Authors: Li Dong , Xu Ziming , Zhang Ke , Zhang Zeyu , Zhou Jinxin , Pan Weijun , Wang Xuan
Published: March 2021

Environmental crosswind can greatly affect the development of aircraft wake vortex pair. Previous numerical simulations and experiments have shown that the nonlinear vertical shear of the crosswind velocity can affect the dissipation rate of the aircraft wake vortex, causing each vortex of the vortex pair descent with different velocity magnitude, which will lead to the asymmetrical settlement and tilt of the wake vortex pair. Through numerical simulations, this article finds that uniform crosswind convection and linear vertical shear crosswind convection can also have an effect on the strength of the vortex. This effect is inversely proportional to the cube of the vortex spacing, so it is more intense on small separation vortex pair. In addition, the superposition of crosswind and vortex-induced velocities will lead to the asymmetrical pressure distribution around the vortex pair, which will also cause the tilt of the vortex pair. Furthermore, a new analysis method for wake vortex is proposed, which can be used to predict the vortex trajectory.
Health Care Expenditures and Financial Burden: A Comparison of Adults in Same-Sex Couples and Different-Sex Couples
Authors: Gavulic Kyle A. , Gonzales Gilbert
Published: March 2021

We used data from the 2014-2017 Medical Expenditure Panel Survey to compare health care expenditures and financial burden between adults in same-sex couples ( n = 514) and adults in different-sex couples ( n = 41,043). Compared with men in different-sex couples ($3,994), men in same-sex couples ($6,896) were more likely to spend more on health care, especially on prescription medications ($2,745 vs. $1,050), which was primarily driven by antiviral medications ($1,061 vs. $35). Women in same-sex couples ($5,886) reported similar health care expenditures compared with women in different-sex couples ($5,619). However, women in same-sex couples were significantly more likely to experience financial burden compared with women in different-sex couples (25.7% vs. 11.3%). We speculate that the disparities reported here are due to a variety of issues, including elevated health needs requiring prescriptions for lesbian, gay, bisexual, and transgender (LGBT) men and lower incomes for LGBT women. More research is needed to understand health services utilization and expenditure patterns among LGBT populations.
Bevacizumab simultaneous combined with dexamethasone implant for treatment of neovascular serous retinal pigment epithelial detachment secondary to neovascular age-related macular degeneration
Authors: Limon Utku , Sezgin Akcay Betül Ilkay
Published: March 2021

Purpose:

To evaluate the add-on effect of simultaneous intravitreal dexamethasone implant to bevacizumab for treatment of neovascular serous retinal pigment epithelial detachment (PED) secondary to neovascular age-related macular degeneration (nAMD).

Methods:

A 72-year-old male patient was previously treated with intravitreal bevacizumab and aflibercept for neovascular serous PED secondary to nAMD. Because of the recurrences in neovascular PED patient was treated with simultaneous intravitreal injection of bevacizumab and dexamethasone implant.

Results:

At the initial visit, the patient’s the best corrected visual acuity (BCVA) in the left eye was 20/800. His left eye had neovascular serous PED with a height of 1100 µm and a largest linear diameter of 3953 µm accompanied by subretinal fluid. He received four intravitreal bevacizumab and five intravitreal aflibercept injections. Although there was a decrease in PED sizes from time to time during the 16-month treatment period, PED height was 926 µm and PED greatest linear diameter was 5820 µm at the end of 16th month. Later, the patient could not have an injection for 3 months (he could not come to his controls during the pandemic period), and when he arrived 3 months later, the PED height was 910 µm and the greatest linear diameter was 5830 µm. With a single simultaneous intravitreal injection of bevacizumab and dexamethasone implant, the PED regressed to 168 µm in height after 3 months. The BCVA increased to 20/200. Any clinical toxic effects did not occur and intraocular pressure did not rise for 3 months after injection.

Conclusion:

Simultaneous intravitreal bevacizumab and dexamethasone implant injection effectively and safely treated treatment-resistant neovascular serous PED. This therapy may be a novel alternative therapy for treatment resistant neovascular serous PED secondary to nAMD. However, further studies are required to understand its effectiveness and safety.
Edgework, Uncertainty, and Social Character
Authors: Mellor Philip A , Shilling Chris
Published: March 2021

This article proposes a novel conceptual understanding of ‘edgework’ – a term denoting the voluntary embrace of risk – by drawing on the long-standing sociological tradition of character studies. In doing so, it addresses the paradox that while first-generation research into high-risk leisure suggested that these activities provided identity-affirming escapes from bureaucratised capitalism, second-generation writings argued that edgework exists in harmony with the norms of ‘risk societies’, raising questions about its continuing appeal. Developing a new analytical perspective with which to assess these views, we argue that the former studies should be understood in the context of challenges to ‘other-directed’ characterological forms prominent within the post-War era, while the latter signal the embodiment of edgework within emergent ‘opportunity-directed’ modalities of social character. This interpretation explains the enduring attractions of edgework alongside its changed social role, and also signals its utility as a prism through which to observe broader characterological changes.
Biomimetic oligopeptide formed enamel-like tissue and dentin tubule occlusion via mineralization for dentin hypersensitivity treatment
Authors: Wang Qing-qing , Wang Siqing , Zhao Tian , Li Yan , Yang Jie , Liu Yumei , Zhang He , Miao Leiying , Sun Weibin
Published: March 2021

Objective:

Dentin hypersensitivity (DH) is a common oral disease with approximately 41.9% prevalence. Reconstruction of dental hard tissues is the preferred treatment for relieving DH. Here, we applied biomineralization method using oligopeptide simulating cementum protein 1 (CEMP1) to regenerate hard tissues on demineralized dentin.

Methods:

The self-assembly and biomineralization property of the oligopeptide were detected by scanning electron microscopy (SEM), circular dichroism spectroscopy, and transmission electron microscopy. Oligopeptide’s binding capacity to demineralized dentin was evaluated by SEM and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). Remineralization was characterized using SEM, ATR-FTIR, X-ray diffraction, and nanoindentation. Oligopeptide’s biocompatibility was evaluated using periodontal ligament cells.

Results:

Oligopeptides self-assembled into nano-matrix and templated mineral precursor formation within 24 h. Moreover, oligopeptide nano-matrix bound firmly on demineralized dentin and resisted water rinsing. Then, bound nano-matrix served as a template to initiate nucleation and transformation of hydroxyapatite on demineralized dentin. After 96 h, oligopeptide nano-matrix regenerated an enamel-like tissue layer with a thickness of 15.35 μm, and regenerated crystals occluded dentin tubules with a depth of 31.27 μm. Furthermore, the oligopeptide nano-matrix had good biocompatibility when co-cultured with periodontal ligament cells.

Conclusions:

This biomimetic oligopeptide simulating CEMP1 effectively induced remineralization and reconstructed hard tissues on demineralized dentin, providing a potential biomaterial for DH treatment.
Development and Practical Application of a Multiple-Criteria Decision Analysis Framework on Respiratory Inhalers: Is It Always Useful in the MOH Malaysia Medicines Formulary Listing Context?
Authors: Yong Yee Vern , Mahamad Dom Siti Hajar , Ahmad Sa’ad Nurulmaya , Lajis Rosliza , Md. Yusof Faridah Aryani , Abdul Rahaman Jamalul Azizi
Published: March 2021

Objectives. The current health technology assessment used to evaluate respiratory inhalers is associated with limitations that have necessitated the development of an explicit formulary decision-making framework to ensure balance between the accessibility, value, and affordability of medicines. This study aimed to develop a multiple-criteria decision analysis (MCDA) framework, apply the framework to potential and currently listed respiratory inhalers in the Ministry of Health Medicines Formulary (MOHMF), and analyze the impacts of applying the outputs, from the perspective of listing and delisting medicines in the formulary. Methods. The overall methodology of the framework development adhered to the recommendations of the ISPOR MCDA Emerging Good Practices Task Force. The MCDA framework was developed using Microsoft Excel 2010 and involved all relevant stakeholders. The framework was then applied to 27 medicines, based on data gathered from the highest levels of available published evidence, pharmaceutical companies, and professional opinions. The performance scores were analyzed using the additive model. The end values were then deliberated by an expert committee. Results. A total of eight main criteria and seven subcriteria were determined by the stakeholders. The economic criterion was weighted at 30%. Among the noneconomic criteria, “patient suitability” was weighted the highest. Based on the MCDA outputs, the expert committee recommended one potential medicine (out of three; 33%) be added to the MOHMF and one existing medicine (out of 24; 4%) be removed/delisted from the MOHMF. The other existing medicines remained unchanged. Conclusions. Although this framework was useful for deciding to add new medicines to the formulary, it appears to be less functional and impactful for the removal/delisting existing medicines from the MOHMF. The generalizability of this conclusion to other formulations remains to be confirmed.
Treatment of Mandibular Non-union Using Patient Specific Crib Cage Plates and Cellular Bone Allograft: A Case Report
Authors: Ryu Brian , Abraham Charles , Polido Waldemar D.
Published: March 2021

A gunshot wound to the mandible frequently creates a comminuted fracture that can be debilitating for the patient and challenging for the surgeon. In some instances, immediate open reduction and rigid fixation is not possible, and closed reduction with intermaxillary fixation is employed. This may lead to non-union or mal-union of the segments. This case report describes the management of mal-union of bilateral comminuted mandibular angle fractures secondary to a gunshot wound injury. The mandibular fractures were repaired using virtually planned patient specific reconstruction plates that included a specially designed crib cage to contain a bone graft. A cellular bone allograft—Vivigen (DePuy Synthes, Warsaw, IN)—was chosen as the bone grafting material. The patient was followed up for 7 months with normal functional status and mouth opening and without pain or signs of infection. This report demonstrates that using a virtually planned crib cage plate with cellular bone allograft can optimize surgical repair and bony healing of comminuted mandible fractures.
Safety and tolerability of eptinezumab in patients with migraine: a pooled analysis of 5 clinical trials
Authors: Smith Timothy R. , Spierings Egilius L. H. , Cady Roger , Hirman Joe , Schaeffler Barbara , Shen Vivienne , Sperling Bjørn , Brevig Thomas , Josiassen Mette Krog , Brunner Elizabeth , Honeywell Loan , Mehta Lahar
Published: March 2021

Background

The humanized anti-CGRP monoclonal antibody eptinezumab has been evaluated in five large-scale clinical trials conducted in patients with migraine. This integrated analysis was conducted to evaluate the comprehensive safety and tolerability of eptinezumab in patients with migraine across these studies.

Methods

Data were pooled from four randomized, double-blind, placebo-controlled studies and the first year of one open-label study.

Results

The pooled population comprised 2867 adults with migraine: eptinezumab,n = 2076 (4797 infusions); placebo,n = 791 (1675 infusions). A total of 1137/2076 (54.8%) patients who received eptinezumab and 414/791 (52.3%) patients who received placebo experienced ≥1 treatment-emergent adverse event (TEAE); rates were similar across eptinezumab dose groups (10–1000 mg). For most patients with TEAEs, the events were mild or moderate in severity and considered unrelated to study drug by the investigators. Thirty infusion-site AEs occurred in 27/2076 (1.3%) patients who received eptinezumab and 7 in 7/791 (0.9%) patients who received placebo. Infusion-site AEs led to infusion interruption in 19/2076 (0.9%) and 5/791 (0.6%) patients in the eptinezumab and placebo groups, respectively. Nasopharyngitis occurred in ≥2% of patients in the eptinezumab 300-mg group and with an incidence of at least 2 percentage points greater than in the placebo group; however, in most patients (eptinezumab, 139/140; placebo 40/41), its occurrence was considered not related to study treatment. Adverse events coded to hypersensitivity occurred for 23/2076 (1.1%) patients treated with eptinezumab and no patients in the placebo group. If additional TEAE terms that could indicate hypersensitivity are considered (e.g., urticaria, flushing/hot flush, rash, and pruritus), hypersensitivity reactions in the two pivotal placebo-controlled phase 3 studies occurred in ≥2% of patients in the eptinezumab 100-mg and 300-mg groups, and the incidence was at least 2 percentage points greater in either of these groups than in the placebo group. Most hypersensitivity reactions were not serious and resolved with standard medical treatment or observation without treatment, usually within 1 day.

Conclusions

In adults with migraine, the intravenous administration of eptinezumab every 12 weeks demonstrated a favorable safety and tolerability profile.

Trial registration

ClinicalTrials.gov (Identifiers:NCT01772524,NCT02275117,NCT02559895,NCT02974153,NCT02985398).
Large-scale labeling and assessment of sex bias in publicly available expression data
Authors: Flynn Emily , Chang Annie , Altman Russ B.
Published: March 2021

Background

Women are at more than 1.5-fold higher risk for clinically relevant adverse drug events. While this higher prevalence is partially due to gender-related effects, biological sex differences likely also impact drug response. Publicly available gene expression databases provide a unique opportunity for examining drug response at a cellular level. However, missingness and heterogeneity of metadata prevent large-scale identification of drug exposure studies and limit assessments of sex bias. To address this, we trained organism-specific models to infer sample sex from gene expression data, and used entity normalization to map metadata cell line and drug mentions to existing ontologies. Using this method, we inferred sex labels for 450,371 human and 245,107 mouse microarray and RNA-seq samples from refine.bio.

Results

Overall, we find slight female bias (52.1%) in human samples and (62.5%) male bias in mouse samples; this corresponds to a majority of mixed sex studies in humans and single sex studies in mice, split between female-only and male-only (25.8% vs. 18.9% in human and 21.6% vs. 31.1% in mouse, respectively). In drug studies, we find limited evidence for sex-sampling bias overall; however, specific categories of drugs, including human cancer and mouse nervous system drugs, are enriched in female-only and male-only studies, respectively. We leverage our expression-based sex labels to further examine the complexity of cell line sex and assess the frequency of metadata sex label misannotations (2–5%).

Conclusions

Our results demonstrate limited overall sex bias, while highlighting high bias in specific subfields and underscoring the importance of including sex labels to better understand the underlying biology. We make our inferred and normalized labels, along with flags for misannotated samples, publicly available to catalyze the routine use of sex as a study variable in future analyses.
Autosomal recessive loci contribute significantly to quantitative variation of male fertility in a dairy cattle population
Authors: Hiltpold Maya , Kadri Naveen Kumar , Janett Fredi , Witschi Ulrich , Schmitz-Hsu Fritz , Pausch Hubert
Published: March 2021

Background

Cattle are ideally suited to investigate the genetics of male fertility. Semen from individual bulls is used for thousands of artificial inseminations for which the fertilization success is monitored. Results from the breeding soundness examination and repeated observations of semen quality complement the fertility evaluation for each bull.

Results

In a cohort of 3881 Brown Swiss bulls that had genotypes at 683,609 SNPs, we reveal four novel recessive QTL for male fertility on BTA1, 18, 25, and 26 using haplotype-based association testing. A QTL for bull fertility on BTA1 is also associated with sperm head shape anomalies. All other QTL are not associated with any of the semen quality traits investigated. We perform complementary fine-mapping approaches using publicly available transcriptomes as well as whole-genome sequencing data of 125 Brown Swiss bulls to reveal candidate causal variants. We show that missense or nonsense variants inSPATA16,VWA3A, ENSBTAG00000006717andENSBTAG00000019919are in linkage disequilibrium with the QTL. Using whole-genome sequence data, we detect strong association (P = 4.83 × 10− 12) of a missense variant (p.Ile193Met) inSPATA16with male fertility. However, non-coding variants exhibit stronger association at all QTL suggesting that variants in regulatory regions contribute to variation in bull fertility.

Conclusion

Our findings in a dairy cattle population provide evidence that recessive variants may contribute substantially to quantitative variation in male fertility in mammals. Detecting causal variants that underpin variation in male fertility remains difficult because the most strongly associated variants reside in poorly annotated non-coding regions.
Transcriptional profiling reveals potential involvement of microvillous TRPM5-expressing cells in viral infection of the olfactory epithelium
Authors: Baxter B. Dnate’ , Larson Eric D. , Merle Laetitia , Feinstein Paul , Polese Arianna Gentile , Bubak Andrew N. , Niemeyer Christy S. , Hassell James , Shepherd Doug , Ramakrishnan Vijay R. , Nagel Maria A. , Restrepo Diego
Published: March 2021

Background

Understanding viral infection of the olfactory epithelium is essential because the olfactory nerve is an important route of entry for viruses to the central nervous system. Specialized chemosensory epithelial cells that express the transient receptor potential cation channel subfamily M member 5 (TRPM5) are found throughout the airways and intestinal epithelium and are involved in responses to viral infection.

Results

Herein we performed deep transcriptional profiling of olfactory epithelial cells sorted by flow cytometry based on the expression of mCherry as a marker for olfactory sensory neurons and for eGFP in OMP-H2B::mCherry/TRPM5-eGFP transgenic mice (Mus musculus). We find profuse expression of transcripts involved in inflammation, immunity and viral infection in TRPM5-expressing microvillous cells compared to olfactory sensory neurons.

Conclusion

Our study provides new insights into a potential role for TRPM5-expressing microvillous cells in viral infection of the olfactory epithelium. We find that, as found for solitary chemosensory cells (SCCs) and brush cells in the airway epithelium, and for tuft cells in the intestine, the transcriptome of TRPM5-expressing microvillous cells indicates that they are likely involved in the inflammatory response elicited by viral infection of the olfactory epithelium.
Diversity and characterization of temperate bacteriophages induced in Pasteurella multocida from different host species
Authors: Abdulrahman Rezheen F. , Davies Robert L.
Published: March 2021

Background

Bacteriophages play important roles in the evolution of bacteria and in the emergence of new pathogenic strains by mediating the horizontal transfer of virulence genes. Pasteurella multocida is responsible for different disease syndromes in a wide range of domesticated animal species. However, very little is known about the influence of bacteriophages on disease pathogenesis in this species.

Results

Temperate bacteriophage diversity was assessed in 47 P. multocida isolates of avian (9), bovine (8), ovine (10) and porcine (20) origin. Induction of phage particles with mitomycin C identified a diverse range of morphological types representing both Siphoviridae and Myoviridae family-types in 29 isolates. Phage of both morphological types were identified in three isolates indicating that a single bacterial host may harbour multiple prophages. DNA was isolated from bacteriophages recovered from 18 P. multocida isolates and its characterization by restriction endonuclease (RE) analysis identified 10 different RE types. Phage of identical RE types were identified in certain closely-related strains but phage having different RE types were present in other closely-related isolates suggesting possible recent acquisition. The host range of the induced phage particles was explored using plaque assay but only 11 (38%) phage lysates produced signs of infection in a panel of indicator strains comprising all 47 isolates. Notably, the majority (9/11) of phage lysates which caused infection originated from two groups of phylogenetically unrelated ovine and porcine strains that uniquely possessed the toxA gene.

Conclusions

Pasteurella multocida possesses a wide range of Siphoviridae- and Myoviridae-type bacteriophages which likely play key roles in the evolution and virulence of this pathogen.
Source–sink manipulations differentially affect carbon and nitrogen dynamics, fruit metabolites and yield of Sacha Inchi plants
Authors: Cai Zhiquan , Xie Tao , Xu Jin
Published: March 2021

Background

Being a promising tropical woody oilseed crop, the evergreen and recurrent plants of Sacha Inchi (Plukenetia volubilis L.) has complex phenology and source–sink interactions. Carbon source–sink manipulations with control and two treatments (reduce source, ca. 10% mature leaf pruning; reduce sink, 10% fruitlet thinning) were conducted on 2.5-year-old field-grown P. volubilis plantation during the early-wet season in a seasonal tropical area.

Results

Leaf photosynthetic rate and specific leaf area largely remained unchanged in response to defoliation or defloration. Compared with control, higher N contents on average were observed in both remaining leaves and branches of the defoliated plants, suggesting that N-mobilization was mainly due to the enhanced N uptake from soil. Carbon, but not N, is a source-driven growth process of P. volubilis plants, as defoliation reduced the contents of non-structural carbohydrates (especially sugar) in branches, although temporally, whereas defloration increased available C reserve. The seasonal dynamic pattern of fruit ripening was altered by source–sink regulations. Total seed yield throughout the growing season, which depends on fruit set and retention (i.e., number of matured fruit) rather than individual fruit development (size), was slightly increased by defloration but was significantly decreased by defoliation. Compared with control, defloration did not enrich the KEGG pathway, but defoliation downregulated the TCA cycle and carbohydrate and lipid metabolisms in fruitlets after 24 days of the applications of source–sink manipulation.

Conclusion

Carbohydrate reserves serve to buffer sink–source imbalances that may result from temporary adjustment in demand for assimilates (e.g., defloration) or shortfalls in carbon assimilation (e.g., defoliation). Defoliation is disadvantageous for the yield and also for carbohydrate and lipid accumulation in fruits of P. volubilis plants. Although more studies are needed, these results provide new insights to the further improvement in seed yield of the strong source-limited P. volubilis plants by source/sink manipulations.
Feasibility and efficacy of modified fixed citrate concentration protocol using only commercial preparations in critically ill patients: a prospective cohort study with a historical control group
Authors: Shi Yan , Qin Han-Yu , Peng Jin-Min , Hu Xiao-Yun , Du Bin
Published: March 2021

Background

The cumbersome program and the shortage of commercial solution hindered the regular application of regional citrate anticoagulation (RCA). It is urgent to simplify the protocol using only commercial preparations. The aim of this study was to explore the feasibility and efficacy of the modified protocol for continuous veno-venous hemofiltration (CVVH) in unselected critically ill patients.

Methods

A prospective cohort study was conducted in 66 patients who received a new protocol combining fixed citrate concentration with modified algorithm for supplements (i.e., fixed protocol), and compared the efficacy, safety and convenience for this group to a historical control group with a traditional protocol (n = 64), where citrate was titrated according to the circuit ionized calcium concentration (i.e., titrated protocol). The convenience was defined as the demand for monitoring test and dose adjustment of any supplement.

Results

The filter lifespan was 63.2 ± 16.1 h in the fixed group and 51.9 ± 17.7 h in the titrated group, respectively. Kaplan-Meier survival analysis demonstrated longer circuit lifetime for fixed group (log-rank,p = 0.026). The incidence of circuit clotting was lower in the fixed protocol (15.2% vs. 29.7% in the titrated protocol,p = 0.047). Moreover, compared with the titrated group, patients with fixed protocol had less demand for monitoring test and dose adjustment of any supplement (the number of times per person per day) (3.3 [IQR 2.3–4.5] vs. 5.7 [IQR 3.3–6.9],p = 0.001 and 1.9 [IQR 0.5–2.7] vs. 6.3 [IQR 4.2–7.9],p < 0.001; respectively). No new onset bleeding complications occurred in all patients. The overall incidence of suspected citrate accumulation was 4.6% and there was no difference between the two groups (p = 0.969), yet a lower rate of metabolic alkalosis was found in the fixed group (3.0% vs. 14.1%,p = 0.024).

Conclusions

Our modified fixed citrate concentration protocol is feasible, safe and effective to enhance the circuit lifespan and the convenience of implementation while maintaining a similar safety when compared to the traditional protocol. Using only commercial preparations may be helpful for widespread application of RCA.

Trial registration

Clinicaltrials.gov.NCT02663960. Registered 26 January 2016.
Comparing the use of aggregate data and various methods of integrating individual patient data to network meta-analysis and its application to first-line ART
Authors: Kanters Steve , Karim Mohammad Ehsanul , Thorlund Kristian , Anis Aslam H. , Zoratti Michael , Bansback Nick
Published: March 2021

Background

The 2018 World Health Organization HIV guidelines were based on the results of a network meta-analysis (NMA) of published trials. This study employed individual patient-level data (IPD) and aggregate data (AgD) and meta-regression methods to assess the evidence supporting the WHO recommendations and whether they needed any refinements.

Methods

Access to IPD from three trials was granted throughClinicalStudyDataRequest.com(CSDR). Seven modelling approaches were applied and compared: 1) Unadjusted AgD network meta-analysis (NMA) – the original analysis; 2) AgD-NMA with meta-regression; 3) Two-stage IPD-AgD NMA; 4) Unadjusted one-stage IPD-AgD NMA; 5) One-stage IPD-AgD NMA with meta-regression (one-stage approach); 6) Two-stage IPD-AgD NMA with empirical-priors (empirical-priors approach); 7) Hierarchical meta-regression IPD-AgD NMA (HMR approach). The first two were the models used previously. Models were compared with respect to effect estimates, changes in the effect estimates, coefficient estimates, DIC and model fit, rankings and between-study heterogeneity.

Results

IPD were available for 2160 patients, representing 6.5% of the evidence base and 3 of 24 edges. The aspect of the model affected by the choice of modeling appeared to differ across outcomes. HMR consistently generated larger intervals, often with credible intervals (CrI) containing the null value. Discontinuations due to adverse events and viral suppression at 96 weeks were the only two outcomes for which the unadjusted AgD NMA would not be selected. For the first, the selected model shifted the principal comparison of interest from an odds ratio of 0.28 (95% CrI: 10.17, 0.44) to 0.37 (95% CrI: 0.23, 0.58). Throughout all outcomes, the regression estimates differed substantially between AgD and IPD methods, with the latter being more often larger in magnitude and statistically significant.

Conclusions

Overall, the use of IPD often impacted the coefficient estimates, but not sufficiently as to necessitate altering the final recommendations of the 2018 WHO Guidelines. Future work should examine the features of a network where adjustments will have an impact, such as how much IPD is required in a given size of network.
A multicentre prospective double blinded randomised controlled trial of intravenous iron (ferric Derisomaltose (FDI)) in Iron deficient but not anaemic patients with chronic kidney disease on functional status
Authors: Bhandari S. , Allgar V. , Lamplugh A. , Macdougall I. , Kalra P. A.
Published: March 2021

Background

Iron deficiency (ID) is common in patients with chronic kidney disease (CKD). Intravenous (IV) iron in heart failure leads to improvement in exercise capacity and improvement in quality-of-life measurements; however, data in patients with CKD are lacking.

Methods

The Iron and the Heart Study was a prospective double blinded randomised study in non-anaemic CKD stages 3b-5 patients with ID which investigated whether 1000 mg of IV iron (ferric derisomaltose (FDI)) could improve exercise capacity in comparison to placebo measured at 1 and 3 months post infusion. Secondary objectives included effects on haematinic profiles and haemoglobin, safety analysis and quality of life questionnaires (QoL).

Results

We randomly assigned 54 patients mean (SD) age for FDI (n = 26) 61.6 (10.1) years vs placebo (n = 28; 57.8 (12.9) years) and mean eGFR (33.2 (9.3) vs. 29.1 (9.6) ml/min/1.73m2) at baseline, respectively. Adjusting for baseline measurements, six-minute walk test (6MWT) showed no statistically significant difference between arms at 1 month (p = 0.736), or 3 months (p = 0.741). There were non-significant increases in 6MWT from baseline to 1 and 3 months in the FDI arm. Haemoglobin (Hb) at 1 and 3 months remained stable. There were statistically significant increases in ferritin (SF) and transferrin saturation (TSAT) at 1 and 3 months (p < 0.001). There was a modest numerical improvement in QoL parameters. There were no adverse events attributable to IV iron.

Conclusion

This study demonstrated a short-term beneficial effect of FDI on exercise capacity, but it was not significant despite improvements in parameters of iron status, maintenance of Hb concentration, and numerical increases in functional capacity and quality of life scores. A larger study will be required to confirm if intravenous iron is beneficial in iron deficient non-anaemic non-dialysis CKD patients without heart failure to improve the 6MWT.

Trial registration

European Clinical Trials Database (EudraCT) No: 2014-004133-16

REC no: 14/YH/1209

Date First Registered: 2015-02-17 and date of end of trail 2015-05-23

Sponsor ref R1766 and Protocol No: IHI 141
Role of suppression of endometriosis with progestins before IVF-ET: a non-inferiority randomized controlled trial
Authors: Khalifa Eissa , Mohammad Hashem , Abdullah Ameer , Abdel-Rasheed Mazen , Khairy Mohammed , Hosni Mahmoud
Published: March 2021

Background

Endometriosis affects the responsiveness to ovarian stimulation. This study aimed to assess the role of Dienogest pretreatment for endometriosis suppression as compared to Gonadotropin-releasing hormone agonist (GnRHa) in patients with endometriosis pursuing IVF treatment.

Methods

In this randomized controlled trial, 134 women with endometriosis-related infertility were randomly allocated to group A (n = 67) who had monthly depot GnRHa for 3 months before ovarian stimulation in IVF treatment (Ultra-long protocol), and Group B (n = 67) who had daily oral Dienogest 2 mg/d for 3 months before starting standard long protocol for IVF. The primary outcome measure was the number of oocytes retrieved. The secondary outcome measures included the number of mature oocytes, fertilization rate, quality of life assessed by FertiQoL scores, cost of treatment, and pregnancy outcomes.

Results

Although there was no statistically significant difference between both groups regarding ovarian stimulation, response parameters, and pregnancy outcomes, the Dienogest group had a lower cost of treatment (2773 vs. 3664 EGP, P < 0.001), lower side effects (29.9% vs. 59.7%, P < 0.001), higher FertiQoL treatment scores (33.2 vs. 25.1, P < 0.001) and higher tolerability scores (14.1 vs. 9.4, P < 0.001 < 0.001).

Conclusion

Our study indicates that Dienogest is a suitable and safe substitute for GnRHa pretreatment in endometriosis patients.

Trial registration

NCT04500743 “Retrospectively registered on August 5, 2020”.
Identification of a novel GPR143 mutation in a large Chinese family with isolated foveal hypoplasia
Authors: Mao Xiying , Chen Mingkang , Yu Yan , Liu Qinghuai , Yuan Songtao , Fan Wen
Published: March 2021

Background

Pathogenic variants of G-protein coupled receptor 143 (GPR143) gene often leads to ocular albinism type I (OA1) characterized by nystagmus, iris and fundus hypopigmentation, and foveal hypoplasia. In this study, we identified a novel hemizygous nonsense mutation in GPR143 that caused an atypical manifestation of OA1.

Case presentation

We reported a large Chinese family in which all affected individuals are afflicted with poor visual acuity and foveal hypoplasia without signs of nystagmus. Fundus examination of patients showed an absent foveal reflex and mild hypopigmentation. The fourth grade of foveal hypoplasia and the reduced area of blocked fluorescence at foveal region was detected in OCT. OCTA imaging showed the absence of foveal avascular zone. In addition, the amplitude of multifocal ERG was reduced in the central ring. Gene sequencing results revealed a novel hemizygous mutation (c.939G > A) in GPR143 gene, which triggered p.W313X. However, no iris depigmentation and nystagmus were observed among both patients and carriers.

Conclusions

In this study, we reported a novel nonsense mutation of GPR143 in a large family with poor visual acuity and isolated foveal hypoplasia without nystagmus, which further expanded the genetic mutation spectrum of GPR143.
Time to detection of anemia and its predictors among children living with HIV at Debre Tabor and University of Gondar Compressive Specialized Hospitals, 2020: a multicentre retrospective follow-up study
Authors: Chanie Ermias Sisay , Feleke Dejen Getanh , Asnakew Sintayehu , GebreEyesus Fisha Alebel , Tesfaw Aragaw , Bayih Wubet Alebachew , Tigabu Agimasie , Anyalem Yared Asmare , Amare Abraham Tsedalu , Belay Demeke Mesfin , Dagnaw Fentaw Teshome , Abate Biruk Beletew
Published: March 2021

Background

Even though antiretroviral therapy access for HIV infected children increased dramatically, anemia have been continued as a challenge regardless of a cluster of differentiation (CD4) count and viral load. Hence, this study aimed to assess the time to detection of anemia and its predictors among children living with HIV at Debre Tabor and university of Gondar compressive specialized hospital, 2020.

Methods

A retrospective follow-up study was conducted from January 2010 to December 2018. A total of 372 children under the age of 15 who had received ART were included in the study. Data were collected from children’s medical charts and ART registration logbook using a standard checklist. Besides, the data were entered into Epi data 4.2.2 and then exported to Stata 14.0 for further analysis. The Cox regression model, the variables having P-value ≤.05 with 95% CIs in multivariable analysis were declared as statistically significant for anemia.

Result

The mean (±SD) of follow-up periods were 56.6 ± 1.7 SD months. The overall median survival time free from anemia was 137 months, and the incidence rate of anemia was 6.9 per 100 PYO (95% CI: 5.3, 7.8). Moreover, WHO clinical staging of III/IV [AHR: 4.2, 95% CI: 1.80, 11.1], low CD4 count below threshold [AHR: 1.9, 95% CI: 1.09, 3.37], cotrimoxazole preventive therapy non-users, and poor level of adherence [(AHR: 2.4, 95% CI: 1.20, 4.85] were the main predictors of the time to detection of anemia.

Conclusion

The incidence rate of anemia in our retrospective cohort was high. The risk of anemia is present in children living with HIV infection but the risk for anemia is increased based on (WHO clinical staging III and IV, CD4 count below the threshold level, CPT non-users, and poor level of adherence). Since many of these risk factors are present routinely, even within one single patient, our clinical monitoring for anemia quarterly was fully justified as was our routine switch from standard therapies such as AZT to another regimen upon lab confirmation of anemia. Additional methods to improve cotrimoxazole preventative therapy and level of adherence are also needed.
Challenge in diagnosis of late onset necrotizing enterocolitis in a term infant: a case report
Authors: Gunadi  , Sirait Dian Nirmala , Fauzi Aditya Rifqi , Nugroho Ninditya , Fahri Fadil , Widitjiarso William , Iskandar Kristy , Nurnaningsih
Published: March 2021

Background

Necrotizing enterocolitis (NEC) is a common devastating inflammatory gastrointestinal disease and frequently occurs in premature infants. Here, we reported a case of late-onset NEC in a term neonate with good outcome after surgery for long-term follow-up.

Case presentation

Ten-week-old male came to emergency unit due to prolonged diarrhea and abdominal distention. He was born at gestational age of 40 weeks with birth weight and Apgar score of 2800 g and 7/8, respectively. He had no history of formula feeding. Two weeks before admitted to the hospital, the patient had frequent diarrhea with fever. He was found lethargic with abdominal distention, absence of bowel sounds and abdominal tenderness. Plain abdominal x-ray and CT scan showed gastric and intestinal dilatation and gasless colon, suggesting a small bowel obstruction, and bowel wall thickening indicating peritonitis, without any free subdiaphragmatic air (pneumoperitoneum). Moreover, the patient did not have a congenital heart disease. While in intensive medical treatment, he showed a continuous clinical deterioration. All findings were suggestive of intestinal inflammation with clinical deterioration, and we decided to perform an emergency exploratory laparotomy and found an ischemia along the jejunoileal with a perforation at 25 cm above the ileocecal valve. Subsequently, we performed a double-barrel ileostomy through a separate incision from the laparotomy. Histopathological findings confirmed the diagnosis of NEC. We closed the stoma at postoperative day 43. The patient was discharged uneventfully a month after stoma closure.

Conclusion

Abdominal CT scan might be useful to establish an early recognition of late-onset NEC; thus, immediate surgical intervention might be performed to decrease its morbidity and mortality. Moreover, late-onset NEC in term neonates might occur without any risk factors or significant co-morbidities.
The relationship between self-harm and bullying behaviour: results from a population based study of adolescents
Authors: Myklestad Ingri , Straiton Melanie
Published: March 2021

Background

This study aims to better understand the association between bullying behaviour (the bullied, the bullies and the bully-victims) and self-harm, and which protective factors moderate this association.

Methods

A total of 16,182 adolescents, aged 12 to 19 years, were invited to participate in the cross-sectional Ung-data survey. This survey covered various aspects of young people’s lives. The response rate was 87%. To assess the relationship between self-harm and bulling behaviour, and psychological- and environmental covariates, we conducted logistic regression analyses. In addition, we tested for potential interaction effects between protective factors and the three bullying groups on self-harm.

Results

Fifteen percent of participating adolescents reported engaging in self-harm during the last year. The risk of self-harm was six times higher for the “bully-victims”, five times higher for the bullied, and three times higher for the bullies, compared to the “neither-bullied nor bullies”. The risk of self-harm in the face of being bullied was significantly greater for girls than boys. Depression, anxiety and parental conflict accounted for some of the association between being bullied and self-harm, and between bully-victims and self-harm. School behavioural problems accounted for some of the association between the bullies and self-harm and the bully-victims and self-harm. The relationship between the bullied and self-harm was significantly moderated by parental support and school well-being, while the relationship between “bully-victims” and self-harm was moderated by school well-being.

Conclusion

There is a strong link between bullying and self-harm. Interventions to address bullying may reduce self-harm. Our findings also suggest that high levels of parental support and school well-being may buffer the harmful relationship between bullying behaviour and self-harm. Addressing these factors may be important in reducing the risk of self-harm among those experiencing bullying.