bluuebunny/crossref_metadata_2025 huggingface dataset:
FUNCTIONAL AND MORPHOLOGICAL OUTCOMES OF THE INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE IN SMALL-SIZED AND MEDIUM-SIZED MACULAR HOLES <400 µm
Authors: Baumann Carmen , Dervenis Nikolaos , Kirchmair Katharina , Lohmann Chris P. , Kaye Stephen B. , Sandinha Maria T.
Published: March 2021

Purpose:

To assess the effect of an internal limiting membrane flap (IF) in macular hole surgery on the best-corrected visual acuity (BCVA) and integrity of the ellipsoid zone (EZ) and external limiting membrane.

Methods:

Patients were included who had successful surgery for macular hole <400 µm with or without an IF. Main outcome measures were BCVA and restoration of the external limiting membrane and EZ at 12 months.

Results:

Sixty patients were included, 36 with conventional peeling and 24 with an IF. The best-corrected visual acuity improved from 0.74 (±0.30) logarithm of the minimum angle of resolution (20/110 Snellen) to 0.26 (±0.20) (20/36 Snellen) in patients without and from 0.77 (±0.32) logarithm of the minimum angle of resolution (20/118 Snellen) to 0.18 (±0.12) (20/30 Snellen) in patients with an IF, respectively. There was no difference in the integrity of the EZ and external limiting membrane in patients with or without an IF at either 3 (P = 0.58, P = 0.20), 6 (P = 0.81, P = 0.10), or 12 months (P = 0.60, P = 0.20) or in the BCVA at 3 (P = 0.24), 6 (P = 0.18) and 12 months (P = 0.11). In the multivariable model, only preoperative BCVA (P < 0.01), EZ integrity (P = 0.001), and age (P < 0.01) were associated with the post-operative BCVA.

Conclusion:

In patients undergoing surgery for macular hole <400 µm, the use of an IF did not affect the BCVA or the integrity of the EZ and external limiting membrane.
Diphtheroids as Corneal Pathogens in Chronic Ocular Surface Disease in Stevens–Johnson Syndrome/Toxic Epidermal Necrolysis
Authors: Shanbhag Swapna S. , Shih Grace , Bispo Paulo J. M. , Chodosh James , Jacobs Deborah S. , Saeed Hajirah N.
Published: March 2021

Purpose:

To characterize diphtheroid corneal infections in eyes in the chronic phase of Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).

Methods:

Observational case series.

Results:

Four eyes of 3 patients were included in this review. Each eye presented with persistent corneal epithelial defect with corneal thinning in the chronic phase of SJS/TEN. None of the epithelial defects were associated with stromal infiltration. The corneas were cultured at the time of workup of persistent epithelial defect (3 eyes) or at time of tectonic penetrating keratoplasty after perforation (1 eye). Cultures yielded abundant growth of Corynebacterium spp., including Corynebacterium jeikeium (n = 2), Corynebacterium glucuronolyticum (n = 1), and a multidrug-resistant Corynebacterium striatum isolate (n = 1). The ocular surface was stabilized with surgical intervention (1 eye) or with introduction of fortified topical antibiotic based on laboratory identification and susceptibility testing of the isolated organisms (3 eyes). Numerous risk factors for microbial keratitis were present in all 4 eyes.

Conclusions:

In eyes with a persistent corneal epithelial defect in the chronic phase of SJS/TEN, even in the absence of an infiltrate, corneal culture should be undertaken. Recognition and treatment of Corynebacterium spp. as opportunistic pathogens may lead to favorable outcomes in cases of clinically sterile ulceration during the chronic phase of SJS/TEN.
Efficacy of Immunosuppressants in High Rejection Risk Keratoplasty: A Meta-Analysis of Comparative Studies
Authors: Yu Kang , Lian Xiu-Fen , Jiang Xiu-Ying , Zhou Shi-You
Published: March 2021

Purpose:

To evaluate the prophylactic effects of immunosuppressants in corneal graft rejection after high-risk penetrating keratoplasty.

Methods:

We searched PubMed, Embase, and the Cochrane Library for comparative studies published between 1989 and 2019 that evaluated the efficacy of immunosuppressants for high-risk corneal graft. The primary outcomes were the 1- and 3-year rejection rates. A fixed-effects or random-effects model was used on the basis of the I
2 value, and the results were reported as odds ratios (ORs) and 95% confidence intervals (CIs).

Results:

Topical tacrolimus (FK506) was more effective than topical cyclosporine A (CsA) at reducing the 1-year graft rejection rate (OR: 0.17; 95% CI, 0.08–0.37, P<0.01). However, the combination of steroid with either topical FK506 (OR: 0.4; 95% CI, 0.16–1.04, P = 0.09) or CsA (OR: 0.74; 95% CI, 0.32–1.71, P= 0.48) did not show significant superiority in preventing immune rejection compared with steroid monotherapy. Mycophenolate mofetil (MMF) was more effective than CsA at reducing the 1-year graft rejection rate (OR: 2.67; 95% CI, 1.50–4.76, P<0.01). However, MMF was not significantly superior to CsA at reducing the 3-year graft rejection rate (OR: 1.21; 95% CI, 0.45–3.25, P = 0.71). For reducing the 1-year rejection rate, MMF (OR: 0.12; 95% CI, 0.03–0.39, P < 0.01) and CsA (OR: 0.28; 95% CI, 0.10–0.76, P = 0.01) were each more effective than the control groups.

Conclusions:

FK506 eye drops, MMF, and systemic CsA were considered to be promising management to prevent rejection in high-risk penetrating keratoplasty in the present study.
Safety and Efficacy of Manual Aspiration Via Small Bore Chest Tube in Facilitating the Outpatient Management of Transbronchial Biopsy-related Iatrogenic Pneumothorax
Authors: Matus Ismael , Mertens Avalon , Wilton Shannon , Raja Haroon , Roedder Timothy
Published: March 2021

Background:

Iatrogenic pneumothorax complicates transbronchial biopsies with a prevalence of 1% to 6%. Conventional treatment consists of inpatient management with chest tube drainage. While aspiration techniques have been investigated in the management of both primary spontaneous and transthoracic lung biopsy-induced pneumothorax, its role in the management of transbronchial biopsy-iatrogenic pneumothorax (TBBX-IP) is undefined. An appealing treatment alternative for TBBX-IP may exist in the placement of a small bore chest tube (SBCT) followed by a manual aspiration (MA) technique promoting earlier SBCT removal to facilitate outpatient management. To our knowledge, no study exists evaluating the efficacy of MA via a SBCT performed specifically for TBBX-IP.

Patients and Methods:

Prospective evaluation of the efficacy of a protocolized pathway incorporating MA through a SBCT for the outpatient management of TBBX-IP. Primary outcome was the clinicoradiographic resolution of TBBX-IP avoiding hospitalizations.

Results:

A total of 763 biopsies performed; 31 complicated by TBBX-IP, 18 qualified for intervention. Sixteen were outpatients, 2 inpatients. Thirteen (81.25%) of the 16 outpatients were successfully treated with MA via SBCT and did not require admission. Twelve (75%) of these 13 had SBCT removed, 1 patient was discharged with SBCT and removed in 24 hours. Of the 18 patients requiring intervention, 13 (72.2%) were successfully treated with MA via SBCT enabling removal of SBCT. No patient required reintervention.

Conclusion:

MA via SBCT represents a safe and viable management approach of TBBX-IP promoting earlier SBCT removal and decreased hospitalizations. Our results challenge conventional management of TBBX-IP warranting further investigation.
Patient Outcomes Associated With Utilization of Education, Case Management, and Advanced Practice Pharmacy Services by American Indian and Alaska Native Peoples With Diabetes
Authors: O’Connell Joan , Reid Margaret , Rockell Jennifer , Harty Kathleen , Perraillon Marcelo , Manson Spero
Published: March 2021

Background:

The burden of diabetes is exceptionally high among American Indian and Alaska Native (AI/AN) peoples. The Indian Health Service (IHS) and Tribal health programs provide education, case management, and advanced practice pharmacy (ECP) services for AI/ANs with diabetes to improve their health outcomes.

Objective:

The objective of this study was to evaluate patient outcomes associated with ECP use by AI/AN adults with diabetes.

Research Design:

This observational study included the analysis of IHS data for fiscal years (FY) 2011–2013. Using propensity score models, we assessed FY2013 patient outcomes associated with FY2012 ECP use, controlling for FY2011 baseline characteristics.

Subjects:

AI/AN adults with diabetes who used IHS and Tribal health services (n=28,578).

Measures:

We compared health status and hospital utilization outcomes for ECP users and nonusers.

Results:

Among adults with diabetes, ECP users, compared with nonusers, had lower odds of high systolic blood pressure [odds ratio (OR)=0.85, P<0.001] and high low-density lipoprotein cholesterol (OR=0.89, P<0.01). Among adults with diabetes absent cardiovascular disease (CVD) at baseline, 3 or more ECP visits, compared with no visits, was associated with lower odds of CVD onset (OR=0.79, P<0.05). Among adults with diabetes and CVD, any ECP use was associated with lower odds of end-stage renal disease onset (OR=0.60, P<0.05). ECP users had lower odds of 1 or more hospitalizations (OR=0.80, P<0.001).

Conclusions:

Findings on positive patient outcomes associated with ECP use by adults with diabetes may inform IHS and Tribal policies, funding, and enhancements to ECP services to reduce disparities between AI/ANs and other populations in diabetes-related morbidity and mortality.
High Expression of PRSS3 Indicates Unfavorable Clinical Outcomes in Colon Adenocarcinoma
Authors: Zhang Quanyi , Wang Jihai , Huang Di , Liu Gang
Published: March 2021

Introduction:

Serine proteases have been implicated as key drivers and facilitators of cancer malignancy. Protease, serine, 3 (PRSS3), which belongs to the serine proteases family, is reported to be abundantly expressed in a variety of types of tumor and contributes to the initiation and development of cancers. However, the clinical role of PRSS3 in colon adenocarcinoma (CAC) was not clarified yet. In the present study, we explored the potential effect of PRSS3 in CAC and whether it is related to the poor survival of CAC patients.

Materials and Methods:

The mRNA and protein levels of PRSS3 were examined in CAC samples and connective noncancerous colon samples through quantitative real-time polymerase chain reaction assay and immunohistochemistry staining. Univariate and multivariate analyses were performed to estimate the prognostic role of PRSS3 in enrolled CAC patients.

Results:

PRSS3 expression in CAC samples was significantly increased compared with connective noncancerous samples. Moreover, a higher level of PRSS3 was found to be correlated with the larger tumor size, advanced T stage, and positive lymph node metastasis. In addition, PRSS3 was also defined as an unfavorable prognosis factor for CAC patients.

Conclusions:

High expression of PRSS3 was significantly related to the unfavorable clinical features and poor prognosis in CAC patients. It suggested that PRSS3 might serve as a novel prognostic indicator and potential drug target for CAC treatment.
Digital Image Analysis of the Proliferation Markers Ki67 and Phosphohistone H3 in Gastroenteropancreatic Neuroendocrine Neoplasms: Accuracy of Grading Compared With Routine Manual Hot Spot Evaluation of the Ki67 Index
Authors: Lea Dordi , Gudlaugsson Einar G. , Skaland Ivar , Lillesand Melinda , Søreide Kjetil , Søreide Jon A.
Published: March 2021

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare epithelial neoplasms. Grading is based on mitotic activity or the percentage of Ki67-positive cells in a hot spot. Routine methods have poor intraobserver and interobserver consistency, and objective measurements are lacking. This study aimed to evaluate digital image analysis (DIA) as an objective assessment of proliferation markers in GEP-NENs. A consecutive cohort of patients with automated DIA measurement of Ki67 (DIA Ki67) and phosphohistone H3 (DIA PHH3) on immunohistochemical slides was analyzed using Visiopharm image analysis software (Hoersholm, Denmark). The results were compared with the Ki67 index from routine pathology reports (pathology Ki67). The study included 159 patients (57% males). The median pathology Ki67 was 2.0% and DIA Ki67 was 4.1%. The interclass correlation coefficient of the DIA Ki67 compared with the pathology Ki67 showed an excellent agreement of 0.96 [95% confidence interval (CI): 0.94-0.96]. The observed kappa value was 0.86 (95% CI: 0.81-0.91) when comparing grades based on the same methods. PHH3 was measured in 145 (91.2%) cases. The observed kappa value was 0.74. (95% CI: 0.65-0.83) when comparing grade based on the DIA PHH3 and the pathology Ki67. The DIA Ki67 shows excellent agreement with the pathology Ki67. The DIA PHH3 measurements were more varied and cannot replace other methods for grading GEP-NENs.
High-grade Transformation/Dedifferentiation in Salivary Gland Carcinomas: Occurrence Across Subtypes and Clinical Significance
Authors: Skalova Alena , Leivo Ilmo , Hellquist Henrik , Agaimy Abbas , Simpson Roderick H.W. , Stenman Göran , Vander Poorten Vincent , Bishop Justin A. , Franchi Alessandro , Hernandez-Prera Juan C. , Slouka David , Willems Stefan M. , Olsen Kerry D. , Ferlito Alfio
Published: March 2021

High-grade transformation (HGT) or dedifferentiation has been described in a variety of salivary gland carcinomas, including acinic cell carcinoma, secretory carcinoma, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma, polymorphous adenocarcinoma, low-grade mucoepidermoid carcinoma, and hyalinizing clear cell carcinoma. High-grade (HG) transformed tumors are composed of a conventional low-grade component characterized by specific microscopic and immunohistochemical features for the given entity, intermingled with or juxtaposed to areas of HG morphology. This is usually either poorly differentiated adenocarcinoma, carcinoma not otherwise specified, or undifferentiated carcinoma, in which the original line of differentiation is lost. The HG component is composed of solid nests of anaplastic cells with large vesicular pleomorphic nuclei, prominent nucleoli, and abundant cytoplasm. Frequent mitoses and extensive necrosis may be present. The Ki-67 labeling index is consistently higher in the HG component. The molecular genetic mechanisms responsible for HGT of salivary gland carcinomas are largely unknown, though p53 inactivation and human epidermal growth factor receptor 2 overexpression and/or gene amplification have been demonstrated in the HG component in a few examples, the frequency varies for each histologic type. Salivary gland carcinomas with HGT are more aggressive than conventional carcinomas, with a higher local recurrence rate and a poorer prognosis. They have a high propensity for cervical lymph node metastasis suggesting a need for a wider resection and neck dissection. HGT of salivary gland carcinoma can occur either at initial presentation or less commonly at the time of recurrence, sometimes following postoperative radiotherapy. The potential for HGT in almost any type of salivary gland carcinoma warrants a thorough sampling of all salivary gland malignancies to prevent oversight of a HG component.
Novel Histologic Classification of Small Tumor Cell Nests for Lung Adenocarcinoma With Prognostic and Etiological Significance
Authors: Saito Ryoko , Ninomiya Hironori , Okumura Sakae , Mun Mingyon , Sasano Hironobu , Ishikawa Yuichi
Published: March 2021

Small tumor cell nests such as micropapillary nests are histologic poor prognostic markers for adenocarcinomas of various organs, including the lung. However, for the lung, the association of micropapillary patterns with smoking is controversial, which may be because of a vague definition of micropapillary patterns. This study clarifies the implications of small tumor cell nests by introducing a new dichotomic classification based on the glandular polarity of tumor cells: pure micropapillary nests (pMPs), preserving glandular polarity, and small solid nests (SSNs), lacking polarity. We examined the clinicopathologic factors in 436 resected adenocarcinomas, and analyzed the overall survival between groups classified by either the presence or absence of pMPs and SSNs. pMP was positively associated with nonsmoking–related features such as epidermal growth factor receptor mutations and thyroid transcription factor 1 expression. By contrast, SSN was positively associated with smoking-related features such as KRAS mutations and hepatocyte nuclear factor-4a expressions. Besides, pMP and SSN were significant and independent indicators of poor prognosis in all stages. SSN was an indicator in stage I too, whereas pMP was not. Furthermore, prognoses of the group with SSN were significantly worse than those of pMP-only group. In conclusion, the present study has revealed 2 completely different patterns of small tumor cell nests in lung adenocarcinoma, the nonsmoking–related pMPs, and the smoking-related SSNs, by considering glandular polarity. MPP should include only pMPs, and SSNs should be in a solid pattern. This novel classification might boast clinical significance as a potent poor prognostic marker as well as a factor reflecting etiological and genetic characters.
Preparation for Hand Surgery Fellowship: A Comparison of Resident Training Pathways
Authors: Drinane James J. , Drolet Brian , Roth Malcolm Z. , Eberlin Kyle R.
Published: March 2021

Background:

Hand surgery is a unique subspecialty in which one can train after completion of either a plastic, orthopedic, or general surgical residency. This study compared hand surgery experience in residency among these different training pathways.

Methods:

The Accreditation Council for Graduate Medical Education case logs of graduating residents in general surgery, orthopedics, and plastic surgery were evaluated for years 2009 through 2018. Cases were grouped according to the Accreditation Council for Graduate Medical Education–defined categories for hand surgery. Comparisons between specialties were made using a one-tail analysis of variance with a 95 percent confidence interval.

Results:

There were 19,159 total residents studied: 11,189 general surgery, 7290 orthopedic, and 1040 plastic surgery. General surgery performed the fewest total hand surgeries per individual resident, while plastic surgery performed the most. Plastic surgery performed more operations than orthopedics in all categories studied including tendon, nerve, amputation, soft tissue, fracture, vascular cases, with p < 0.01 for each category.

Conclusions:

There are significant differences in the preparation of resident trainees for entry into a hand surgery fellowship, and the lack of uniform exposure to hand surgery represents an opportunity for improvement. Fellowship directors and the tripartite specialty board should embrace the differences among general surgery, orthopedic, and plastic surgery graduates early in the fellowship year and address the expected differences. Trainees’ education should be optimized on an individualized basis with targeted education, additional educational courses, and encouraging trainees to seek out clinical challenges to foster their continued professional growth.
Vitamin K2 protects against Aβ42-induced neurotoxicity by activating autophagy and improving mitochondrial function in Drosophila
Authors: Lin Xiaohui , Wen Xueyi , Wei Zaiwa , Guo Keyi , Shi Fang , Huang Tingting , Wang Wenjing , Zheng Jinou
Published: March 2021

Objective

Alzheimer disease is characterized by progressive decline in cognitive function due to neurodegeneration induced by accumulation of Aβ and hyperphosphorylated tau protein. This study was conducted to explore the protective effect of vitamin K2 against Aβ42-induced neurotoxicity.

Methods

Alzheimer disease transgenic Drosophila model used in this study was amyloid beta with the arctic mutation expressed in neurons. Alzheimer disease flies were treated with vitamin K2 for 28 days after eclosion. Aβ42 level in brain was detected by ELISA. Autophagy-related genes and NDUFS3, the core subunit of mitochondrial complex I, were examined using real-Time PCR (RT-PCR) and western blot analysis.

Results

Vitamin K2 improved climbing ability (P = 0.0105), prolonged lifespan (P < 0.0001) and decreased Aβ42 levels (P = 0.0267), upregulated the expression of LC3 and Beclin1(P = 0.0012 and P = 0.0175, respectively), increased the conversion of LC3I to LC3II (P = 0.0206) and decreased p62 level (P =0.0115) in Alzheimer disease flies. In addition, vitamin K2 upregulated the expression of NDUFS3 (P = 0.001) and increased ATP production (P = 0.0033) in Alzheimer disease flies.

Conclusion

It seems that vitamin K2 protect against Aβ42-induced neurotoxicity by activation of autophagy and rescue mitochondrial dysfunction, which suggests that it may be a potential valuable therapeutic approach for Alzheimer disease.
Thalamic shape abnormalities in patients with multiple sclerosis-related fatigue
Authors: Saberi Amin , Abdolalizadeh AmirHussein , Mohammadi Esmaeil , Nahayati Mohammad A. , Bagheri Hamed , Shekarchi Babak , Kargar Jalal
Published: March 2021

Thalamus plays an important role in the pathogenesis of multiple sclerosis-related fatigue (MSrF). However, the thalamus is a heterogeneous structure and the specific thalamic subregions that are involved in this condition are unclear. Here, we used thalamic shape analysis for the detailed localization of thalamic abnormalities in MSrF. Using the Modified Fatigue Impact Scale, we measured fatigue in 42 patients with relapsing-remitting multiple sclerosis (MS). The thalamic shape was extracted from T1w images using an automated pipeline. We investigated the association of thalamic surface deviations with the severity of global fatigue and its cognitive, physical and psychosocial subdomains. Cognitive fatigue was correlated with an inward deformity of the left anteromedial thalamic surface, but no other localized shape deviation was observed in correlation with global, physical or psychosocial fatigue. Our findings indicate that the left anteromedial thalamic subregions are implicated in cognitive fatigue, possibly through their role in reward processing and cognitive and executive functions.
Deferoxamine reduces amyloid-beta peptides genesis and alleviates neural apoptosis after traumatic brain injury
Authors: Zhaba Wang-Dui , Deji Qu-Zhen , Gao Sheng-Qing , Han Yan-Ling , Gao Chao-Chao , Deng Hong-Ji , Liu Xi-Lin , Li Tao , Zhou Meng-Liang
Published: March 2021

Traumatic brain injury (TBI) is recognized as the most influential risk factor for neurodegenerative diseases later in life, including Alzheimer’s disease. The aberrant genesis of amyloid-β peptides, which is triggered by TBI, is associated with the development of Alzheimer’s disease. Evidence suggests that iron plays a role in both the production of amyloid-β and its neurotoxicity, and iron overload has been noted in the brain after TBI. We therefore investigated the effects of an iron-chelating treatment on amyloid-β genesis in a weight-drop model of TBI in mice. Human brain samples were obtained from patients undergoing surgery for severe brain trauma. The Institute of Cancer Research mice were treated with deferoxamine by intraperitoneal injection after TBI induction. Changes in amyloid-β(1–42) were assessed using western blot and immunohistochemical staining. Ferritin was also detected using western blot to investigate iron deposition in the mice brain. Immunofluorescent terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling was also performed to evaluate neural apoptosis. The amyloid-β(1–42) was markedly elevated after TBI in both humans and mice. Deferoxamine treatment in mice significantly decreased the levels of both amyloid-β(1–42) and ferritin in the brain, and reduced TBI-induced neural cell apoptosis. The iron chelator deferoxamine can alleviate the increase of amyloid-β(1–42) in the brain after TBI, and may therefore be a potential therapeutic strategy to prevent TBI patients from undergoing neurodegenerative processes.
Antisense oligonucleotides targeting alternative splicing of Nrcam exon 10 suppress neurite outgrowth of ganglion sensory neurons in vitro
Authors: Tian Lixia , Chen Yu , Chang Shuyang , Xu Linping , Zhou Xiaoqiong , Mao Qingxiang , Liang Lingli
Published: March 2021

Neuron-glial-related cell adhesion molecule (NrCAM) is a neuronal cell adhesion molecule that has been shown to be involved in several cellular processes in the peripheral nervous system, including neurite outgrowth. We recently reported that alternative splicing of Nrcam mRNA at exon 10 in the dorsal root ganglion (DRG) contributes to the peripheral mechanism of neuropathic pain. Specially, Nrcam antisense oligonucleotides (ASO) targeting Nrcam exon 10, attenuated neuropathic pain hypersensitivities in mice. Here, we investigated the effect of Nrcam ASO on neurite outgrowth of DRG neurons in vitro. By immunostaining DRG neurons with different DRG markers, Nrcam ASO significantly reduced neurite lengths in neurofilament 200-, calcitonin gene–related peptide and isolectin B4–positive neurons in primary DRG neuronal culture. Moreover, Nrcam ASO activates epidermal growth factor receptor, which may mediate the effect of Nrcam ASO on neurite outgrowth of cultured DRG neurons. These results provide evidence that Nrcam ASO suppresses neurite outgrowth in DRG neurons by regulating alternative splicing of Nrcam gene at exon 10 and activation of epidermal growth factor receptor signaling, indicating the differential roles of NrCAM variants/isoforms in neurite outgrowth.
Effect of
Bacillus thuringiensis
biomass and insecticidal activity by cultivation with vegetable wastes
Authors: Pan Xiaohong , Huang Tengzhou , Fang Yun , Rao Wenhua , Guo Xueping , Nie Danyue , Zhang Dingyang , Cao Fang , Guan Xiong , Chen Zhi
Published: March 2021

Bacillus thuringiensis
(Bt) has been regarded as a biopesticide with high efficiency and safety, while it still cannot be popularized and mass-produced because of its high production costs. In the present study, we aimed to develop a cost-effective biopesticide via the secondary use of discharged vegetable wastes as the raw fermentation medium, and the insecticidal activity of Bt strain prepared by this cheap cultivation approach was evaluated. The suitable carbon source, nitrogen source additives and optimal metal ions were screened by the single-factor test, and the optimal combination of additives was determined by orthogonal test and ANOVA analysis. We found that soluble starch (6 g l
−1
), soya bean meal (6 g l
−1
), Al
3+
(0.4 g l
−1
) and Fe
2+
(0.4 g l
−1
) were the optimal exogenous additives, and the optimal fermentation conditions were as follows: pH 7.0, temperature of 35°C and aeration of 80 ml/250 ml. Meanwhile, the bioactivity test results showed that the Bt strain prepared by cheap cultivation still exhibited a good insecticidal effect on
Helicoverpa armigera
compared with the standard LB medium. Collectively, our findings provided a new strategy for vegetable waste utilization with less environmental impact and reduced production cost.
Ocean-wide genomic variation in Gray's beaked whales,
Mesoplodon grayi
Authors: Westbury M. V. , Thompson K. F. , Louis M. , Cabrera A. A. , Skovrind M. , Castruita J. A. S. , Constantine R. , Stevens J. R. , Lorenzen E. D.
Published: March 2021

The deep oceans of the Southern Hemisphere are home to several elusive and poorly studied marine megafauna. In the absence of robust observational data for these species, genetic data can aid inferences on population connectivity, demography and ecology. A previous investigation of genetic diversity and population structure in Gray's beaked whale (
Mesoplodon grayi
) from Western Australia and New Zealand found high levels of mtDNA diversity, no geographic structure and stable demographic history. To further investigate phylogeographic and demographic patterns across their range, we generated complete mitochondrial and partial nuclear genomes of 16 of the individuals previously analysed and included additional samples from South Africa (
n
= 2) and South Australia (
n
= 4), greatly expanding the spatial range of genomic data for the species. Gray's beaked whales are highly elusive and rarely observed, and our data represents a unique and geographically broad dataset. We find relatively high levels of diversity in the mitochondrial genome, despite an absence of population structure at the mitochondrial and nuclear level. Demographic analyses suggest these whales existed at stable levels over at least the past 1.1 million years, with an approximately twofold increase in female effective population size approximately 250 thousand years ago, coinciding with a period of increased Southern Ocean productivity, sea surface temperature and a potential expansion of suitable habitat. Our results suggest that Gray's beaked whales are likely to be resilient to near-future ecosystem changes, facilitating their conservation. Our study demonstrates the utility of low-effort shotgun sequencing in providing ecological information on highly elusive species.
Design of an acoustic energy distributor using thin resonant slits
Authors: Chesnel Lucas , Nazarov Sergei A.
Published: March 2021

We consider the propagation of time-harmonic acoustic waves in a device made of
three unbounded channels connected by thin slits. The wavenumber is chosen such
that only one mode can propagate. The main goal of this work is to present a
device which can serve as an energy distributor. More precisely, the geometry is
first designed so that for an incident wave coming from one channel, the energy
is almost completely transmitted in the two other channels. Additionally,
adjusting slightly two geometrical parameters, we can control the ratio of
energy transmitted in the two channels. The approach is based on asymptotic
analysis for thin slits around resonance lengths. We also provide numerical
results to illustrate the theory.
Genome-wide markers redeem the lost identity of a heavily managed gamebird
Authors: Forcina Giovanni , Tang Qian , Cros Emilie , Guerrini Monica , Rheindt Frank E. , Barbanera Filippo
Published: March 2021

Heavily managed wildlife may suffer from genetic homogenization and reshuffling of locally adapted genotypes with non-native ones. This phenomenon often affects natural populations by reducing their evolutionary potential and speeding up the ongoing biodiversity crisis. For decades, the red-legged partridge (Alectoris rufa), an intensively managed gamebird of conservation concern and considerable socio-economic importance, has been subjected to extensive releases of farm-reared hybrids with the chukar partridge (Alectoris chukar) and translocations irrespective of subspecific affinity. These practices have led to serious concerns that the genetic integrity and biogeographic structure of most red-legged partridge populations are irreversibly affected, as suggested by previous studies based on few genetic markers. Using over 168 000 genome-wide loci and a sampling across the entireA. rufarange, we detected unexpectedly limited and spatially uneven chukar introgression as well as significant intraspecific structure. We demonstrate that species widely feared to have irretrievably lost their genetic identity are likely to be much less affected by unsuitable management practices than previously assumed. Our results spell the need for a radical re-think on animal conservation, possibly restoring native status to populations long treated as compromised. Our study exemplifies how the application of innovative conservation-genomic methods is key to solving wildlife management problems dealing with introgressive hybridization worldwide.
Phylogenetic context of Shiga toxin-producing Escherichia coli serotype O26:H11 in England
Authors: Dallman Timothy J. , Greig David R. , Gharbia Saheer E. , Jenkins Claire
Published: March 2021

The increasing use of PCR for the detection of gastrointestinal pathogens in hospital laboratories in England has improved the detection of Shiga toxin-producing

Escherichia coli

(STEC), and the diagnosis of haemolytic uraemic syndrome (HUS). We aimed to analyse the microbiological characteristics and phylogenetic relationships of STEC O26:H11, clonal complex (CC) 29, in England to inform surveillance, and to assess the threat to public health. There were 502 STEC belonging to CC29 isolated between 2014 and 2019, of which 416 were from individual cases. The majority of isolates belonged to one of three major sequence types (STs), ST16 (n=37), ST21 (n=350) and ST29 (n=24). ST16 and ST29 were mainly isolated from cases reporting recent travel abroad. Within ST21, there were three main clades associated with domestic acquisition. All three domestic clades had Shiga toxin subtype gene (stx) profiles associated with causing severe clinical outcomes including STEC-HUS, specifically either stx1a, stx2a or stx1a/stx2a. Isolates from the same patient, same household or same outbreak with an established source for the most part fell within 5-SNP single linkage clusters. There were 19 5-SNP community clusters, of which six were travel-associated and one was an outbreak of 16 cases caused by the consumption of contaminated salad leaves. Of the remaining 12 clusters, 9/12 were either temporally or geographically related or both. Exposure to foodborne STEC O26:H11 ST21 capable of causing severe clinical outcomes, including STEC-HUS, is an emerging risk to public health in England. The lack of comprehensive surveillance of this STEC serotype is a concern, and there is a need to expand the implementation of methods capable of detecting STEC in local hospital settings.
Genome-wide study of DNA methylation in Amyotrophic Lateral Sclerosis identifies differentially methylated loci and implicates metabolic, inflammatory and cholesterol pathways
Authors: Hop Paul J. , Zwamborn Ramona A.J. , Hannon Eilis , Shireby Gemma L. , Nabais Marta F. , Walker Emma M. , van Rheenen Wouter , van Vugt Joke J.F.A. , Dekker Annelot M. , Westeneng Henk-Jan , Tazelaar Gijs H.P. , van Eijk Kristel R. , Moisse Matthieu , Baird Denis , Khleifat Ahmad Al , Iacoangeli Alfredo , Ticozzi Nicola , Ratti Antonia , Cooper-Knock Jonathan , Morrison Karen E. , Shaw Pamela J. , Basak A. Nazli , Chiò Adriano , Calvo Andrea , Moglia Cristina , Canosa Antonio , Brunetti Maura , Grassano Maurizio , Gotkine Marc , Lerner Yossef , Zabari Michal , Vourc’h Patrick , Corcia Philippe , Couratier Philippe , Mora Pardina Jesus S. , Salas Teresa , Dion Patrick , Ross Jay P. , Henderson Robert D. , Mathers Susan , McCombe Pamela A. , Needham Merrilee , Nicholson Garth , Rowe Dominic B. , Pamphlett Roger , Mather Karen A. , Sachdev Perminder S. , Furlong Sarah , Garton Fleur C. , Henders Anjali K. , Lin Tian , Ngo Shyuan T. , Steyn Frederik J. , Wallace Leanne , Williams Kelly L. ,   BIOS Consortium,   Brain MEND Consortium, Neto Miguel Mitne , Cauchi Ruben J. , Blair Ian P. , Kiernan Matthew C. , Drory Vivian , Povedano Monica , de Carvalho Mamede , Pinto Susana , Weber Markus , Rouleau Guy , Silani Vincenzo , Landers John E. , Shaw Christopher E. , Andersen Peter M. , McRae Allan F. , van Es Michael A. , Pasterkamp R. Jeroen , Wray Naomi R. , McLaughlin Russell L. , Hardiman Orla , Kenna Kevin P. , Tsai Ellen , Runz Heiko , Al-Chalabi Ammar , van den Berg Leonard H. , Damme Philip Van , Mill Jonathan , Veldink Jan H.
Published: March 2021

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability of around 50%. DNA methylation patterns can serve as biomarkers of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study (EWAS) meta-analysis in 10,462 samples (7,344 ALS patients and 3,118 controls), representing the largest case-control study of DNA methylation for any disease to date. We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We show that DNA-methylation-based proxies for HDL-cholesterol, BMI, white blood cell (WBC) proportions and alcohol intake were independently associated with ALS. Integration of these results with our latest GWAS showed that cholesterol biosynthesis was causally related to ALS. Finally, we found that DNA methylation levels at several DMPs and blood cell proportion estimates derived from DNA methylation data, are associated with survival rate in patients, and could represent indicators of underlying disease processes.
Epicardial adipose tissue thickness is associated with increased COVID-19 severity and mortality
Authors: Mehta Roopa , Bello-Chavolla Omar Yaxmehen , Mancillas-Adame Leonardo , Rodriguez-Flores Marcela , Pedraza Natalia Ramírez , Encinas Bethsabel Rodríguez , Pérez Carrión Carolina Isabel , Jasso Ávila María Isabel , Valladares-García Jorge Carlos , Vanegas-Cedillo Pablo Esteban , Juárez Diana Hernández , Vargas-Vázquez Arsenio , Antonio-Villa Neftali Eduardo , Chapa-Ibarguengoitia Monica , Almeda-Valdés Paloma , Elias-Lopez Daniel , Galindo-Fraga Arturo , Gulias-Herrero Alfonso , de Leon Alfredo Ponce , Sifuentes-Osornio José , Aguilar-Salinas Carlos A.
Published: March 2021

BACKGROUND

Increased adiposity and visceral obesity have been linked to adverse COVID-19 outcomes. The amount of epicardial adipose tissue (EAT) may have relevant implications given its proximity to the heart and lungs. Here, we explored the role of EAT in increasing the risk for COVID-19 adverse outcomes.

METHODS

We included 748 patients with COVID-19 attending a reference center in Mexico City. EAT thickness, sub-thoracic and extra-pericardial fat were measured using thoracic CT scans. We explored the association of each thoracic adipose tissue compartment with COVID-19 mortality and severe COVID-19 (defined as mortality and need for invasive mechanical ventilation), according to the presence or absence of obesity. Mediation analyses evaluated the role of EAT in facilitating the effect of age, body mass index and cardiac troponin levels with COVID-19 outcomes.

RESULTS

EAT thickness was associated with increased risk of COVID-19 mortality (HR 1.18, 95%CI 1.01-1.39) independent of age, gender, comorbid conditions and BMI. Increased EAT was associated with lower SpO2 and PaFi index and higher levels of cardiac troponins, D-dimer, fibrinogen, C-reactive protein, and 4C severity score, independent of obesity. EAT mediated 13.1% (95%CI 3.67-28.0%) and 5.1% (95%CI 0.19-14.0%) of the effect of age and 19.4% (95%CI 4.67-63.0%) and 12.8% (95%CI 0.03-46.0%) of the effect of BMI on requirement for intubation and mortality, respectively. EAT also mediated the effect of increased cardiac troponins on myocardial infarction during COVID-19.

CONCLUSION

EAT is an independent risk factor for severe COVID-19 and mortality independent of obesity. EAT partly mediates the effect of age and BMI and increased cardiac troponins on adverse COVID-19 outcomes.
The Effect of Famotidine on Hospitalized Patients with COVID-19: a Systematic Review and Meta-analysis
Authors: Chiu Leonard , Shen Max , Chow Ronald , Lo Chun-Han , Chiu Nicholas , Chen Austin , Shin Hyun Joon , Prsic Elizabeth Horn , Hur Chin , Lebwohl Benjamin
Published: March 2021

Introduction

Famotidine is a competitive histamine H2-receptor antagonist most commonly used for gastric acid suppression but thought to have potential efficacy in treating patients with COVID-19. The aims of this systematic review and meta-analysis are to summarize the current literature and report clinical outcomes on the use of famotidine for treatment of hospitalized patients with COVID-19.

Methods

Five databases were searched through February 12, 2021 to identify observational studies that reported on associations of famotidine use with outcomes in COVID-19. Meta-analysis was conducted for composite primary clinical outcome (e.g. rate of death, intubation, or intensive care unit admissions) and death separately, where either aggregate odds ratio (OR) or hazard ratio (HR) was calculated.

Results

Four studies, reporting on 46,435 total patients and 3,110 patients treated with famotidine, were included in this meta-analysis. There was no significant association between famotidine use and composite outcomes in patients with COVID-19: HR 0.63 (95% CI: 0.35, 1.16). Across the three studies that reported mortality separated from other endpoints, there was no association between famotidine use during hospitalization and risk of death - HR 0.67 (95% CI: 0.26, 1.73) and OR 0.79 (95% CI: 0.19, 3.34). Heterogeneity ranged from 83.69% to 88.07%.

Conclusion

Based on the existing observational studies, famotidine use is not associated with a reduced risk of mortality or combined outcome of mortality, intubation, and/or intensive care services in hospitalized individuals with COVID-19, though heterogeneity was high, and point estimates suggested a possible protective effect for the composite outcome that may not have been observed due to lack of power. Further RCTs may help determine the efficacy and safety of famotidine as a treatment for COVID-19 patients in various care settings of the disease.
Improved Prediction of COVID-19 Transmission and Mortality Using Google Search Trends for Symptoms in the United States
Authors: Alruily Meshrif , Ezz Mohamed , Mostafa Ayman Mohamed , Yanes Nacim , Abbas Mostafa , EL-Manzalawy Yasser
Published: March 2021

Accurate forecasting of emerging infectious diseases can guide public health officials in making appropriate decisions related to the allocation of public health resources. Due to the exponential spread of the COVID-19 infection worldwide, several computational models for forecasting the transmission and mortality rates of COVID-19 have been proposed in the literature. To accelerate scientific and public health insights into the spread and impact of COVID-19, Google released the Google COVID-19 search trends symptoms open-access dataset. Our objective is to develop 7 and 14 -day-ahead forecasting models of COVID-19 transmission and mortality in the US using the Google search trends for COVID-19 related symptoms. Specifically, we propose a stacked long short-term memory (SLSTM) architecture for predicting COVID-19 confirmed and death cases using historical time series data combined with auxiliary time series data from the Google COVID-19 search trends symptoms dataset. Considering the SLSTM networks trained using historical data only as the base models, our base models for 7 and 14 -day-ahead forecasting of COVID cases had the mean absolute percentage error (MAPE) values of 6.6% and 8.8%, respectively. On the other side, our proposed models had improved MAPE values of 3.2% and 5.6%, respectively. For 7 and 14 -day-ahead forecasting of COVID-19 deaths, the MAPE values of the base models were 4.8% and 11.4%, while the improved MAPE values of our proposed models were 4.7% and 7.8%, respectively. We found that the Google search trends for “pneumonia,” “shortness of breath,” and “fever” are the most informative search trends for predicting COVID-19 transmission. We also found that the search trends for “hypoxia” and “fever” were the most informative trends for forecasting COVID-19 mortality.
Reporting results of diagnostic NGS-based testing – user-centered redesign of the clinical report
Authors: Agafonov Oleg , Vik Sigrun , Kjølås Kaja O. , Alagaratnam Sharmini
Published: March 2021

1

Abstract

The transition of next-generation sequencing (NGS) from the research environment to clinical diagnostics has proven difficult, with exome and whole genome sequencing at various stages of implementation in Nordic hospitals. The clinical genomics report details key findings from the interpretation of NGS data and represents the core hand-off between specialized clinical genomics laboratories and the broader healthcare community. However, these text-heavy reports can be difficult to read: critical information may be scattered around the report, and vital information such as limitations of the test may not always be present. Misunderstanding of results, limitations or key findings can lead to incorrect therapeutic decisions, directly impacting patient management.

We applied the principles of user-centred design to redesign clinical reports to respond to user needs, while also incorporating existing recommendations and guidelines. We performed several rounds of needs gathering, first with producers of clinical genetics reports, then with clinicians with various level of experience in genetic testing. Based on the insights from a workshop and interviews, we created prototypes of reports which were evaluated in comparison to a set of simulated reports representing those currently in clinical production. Our results showed that the majority of evaluators found the redesigned reports to be clearer and easier to process, demonstrating the value of this approach.
Quit attempts and tobacco abstinence in primary care patients: long-term follow-up of a pragmatic, two-arm cluster randomised controlled trial on brief stop-smoking advice (ABC versus 5As method)
Authors: Kastaun Sabrina , Viechtbauer Wolfgang , Leve Verena , Hildebrandt Jaqueline , Funke Christian , Klosterhalfen Stephanie , Lubisch Diana , Reddemann Olaf , Raupach Tobias , Wilm Stefan , Kotz Daniel
Published: March 2021

We developed a 3.5-h-training for general practitioners (GPs) in delivering brief stop-smoking advice according to different methods (ABC, 5As). In a pragmatic, cluster randomised controlled trial our training proved effective in increasing GP-delivered rates of such advice. In this follow-up analysis we examined the effect of ABC and 5As on patient-reported quit attempts and point prevalence abstinence at weeks 4, 12, and 26 following GP consultation.

Follow-up data were collected by questionnaires delivered to 1,937 smoking patients recruited before or after the training in which 69 GPs participated. At week 26, ∼70% of the patients were lost to follow-up. All 1,937 smoking patients were included in an intention-to-treat analysis. Multiple imputation was used to impute missing outcome data of each follow-up and few missing data of potential confounders.

While the receipt of brief GP advice compared to no advice was associated with a two-fold increase in patients’ attempts to quit at each follow-up and abstinence at week 26, quit attempts and abstinence rates did not differ significantly from pre- to post-training or between patients from the ABC versus the 5As group.

We previously reported that our training increases patient-reported rates of GP-delivered stop-smoking advice. The present follow-up analysis did not show that patients more often attempted or achieved to quit when they received advice from a trained vs. untrained GP. Future training studies should take contextual factors into account – such as access to free evidence-based cessation treatment – which might hamper the transfer of GPs’ effective advice into patients’ behaviour change.

TRIAL REGISTRATION

German Clinical Trials Register, prior to the first patient in (DRKS00012786, www.drks.de/drks_web/setLocale_EN.do).