bluuebunny/crossref_metadata_2025 huggingface dataset:
Extended spectrum β lactamase-producing Enterobacteriaceae shedding by race horses in Ontario, Canada
Authors: Shnaiderman-Torban Anat , Navon-Venezia Shiri , Paitan Yossi , Archer Holly , Abu Ahmad Wiessam , Bonder Darryl , Hanael Erez , Nissan Israel , Zizelski Valenci Gal , Weese Scott J. , Steinman Amir
Published: December 2020

Background

We aimed to investigate the prevalence, molecular epidemiology and prevalence factors for Extended Spectrum β-Lactamase-producing Enterobacteriaceae (ESBL-E) shedding by race horses. A cross-sectional study was performed involving fecal samples collected from 169 Thoroughbred horses that were housed at a large racing facility in Ontario, Canada. Samples were enriched, plated on selective plates, sub-cultured to obtain pure cultures and ESBL production was confirmed. Bacterial species were identified and antibiotic susceptibility profiles were assessed. E. coli sequence types (ST) and ESBL genes were determined using multilocus sequence type (MLST) and sequencing. Whole genome sequencing was performed to isolates harboring CTX-M-1 gene. Medical records were reviewed and associations were investigated.

Results

Adult horses (n = 169), originating from 16 different barns, were sampled. ESBL-E shedding rate was 12% (n = 21/169, 95% CI 8–18%); 22 ESBL-E isolates were molecularly studied (one horse had two isolates). The main species was E. coli (91%) and the major ESBL gene was CTX-M-1 (54.5%). Ten different E. coli STs were identified. Sixty-four percent of total isolates were defined as multi-drug resistant. ESBL-E shedding horses originated from 8/16 different barns; whereas 48% (10/21) of them originated from one specific barn. Overall, antibiotic treatment in the previous month was found as a prevalence factor for ESBL-E shedding (p = 0.016, prevalence OR = 27.72, 95% CI 1.845–416.555).

Conclusions

Our findings demonstrate the potential diverse reservoir of ESBL-E in Thoroughbred race horses. Multi-drug resistant bacteria should be further investigated to improve antibiotic treatment regimens and equine welfare.
Strategic supplementation of Flemingia silage to enhance rumen fermentation efficiency, microbial protein synthesis and methane mitigation in beef cattle
Authors: Viennasay Bounnaxay , Wanapat Metha
Published: December 2020

Background

Good quality protein as an on-farm feed resource has been in great demand to support the productivity of ruminants. A digestion trial using beef cattle crossbreds was conducted to assess the four dietary treatments of Flemingia macrophylla silage (FMS) supplementation at 0, 0.2, 0.4 and 0.6 kg dry matter (DM)/day in a 4 × 4 Latin square design. Feed DM intakes were measured during the 14 days and sample of feeds, feces, urine, as well as rumen fluid and blood were collected during the 7 days while the animals were on metabolism crates.

Results

Based on this experiment strategic supplementation of FMS increased (P < 0.05) nutrients digestibility (organic matter, crude protein, and acid detergent fiber) enhanced rumen total volatile fatty acid production especially propionic acid (C3), C2:C3 ratio while, remarkably promoted the microbial protein synthesis (MPS) by increasing N-balance and retention of purine derivatives.

Conclusions

Under this experiment, the results revealed the potential use of FMS as a good-quality feed to improve nutrients digestibility, rumen fermentation, microbial protein synthesis, and to mitigate methane production. FMS supplementation at 0.6 kg DM/day exhibited the best result.
Engineering Lactococcus lactis as a multi-stress tolerant biosynthetic chassis by deleting the prophage-related fragment
Authors: Qiao Wanjin , Qiao Yu , Liu Fulu , Zhang Yating , Li Ran , Wu Zhenzhou , Xu Haijin , Saris Per Erik Joakim , Qiao Mingqiang
Published: December 2020

Background

In bioengineering, growth of microorganisms is limited because of environmental and industrial stresses during fermentation. This study aimed to construct a nisin-producing chassis Lactococcus lactis strain with genome-streamlined, low metabolic burden, and multi-stress tolerance characteristics.

Results

The Cre-loxP recombination system was applied to reduce the genome and obtain the target chassis strain. A prophage-related fragment (PRF; 19,739 bp) in the L. lactis N8 genome was deleted, and the mutant strain L. lactis N8-1 was chosen for multi-stress tolerance studies. Nisin immunity of L. lactis N8-1 was increased to 6500 IU/mL, which was 44.44% higher than that of the wild-type L. lactis N8 (4500 IU/mL). The survival rates of L. lactis N8-1 treated with lysozyme for 2 h and lactic acid for 1 h were 1000- and 10,000-fold higher than that of the wild-type strain, respectively. At 39 ℃, the L. lactis N8-1 could still maintain its growth, whereas the growth of the wild-type strain dramatically dropped. Scanning electron microscopy showed that the cell wall integrity of L. lactis N8-1 was well maintained after lysozyme treatment. Tandem mass tags labeled quantitative proteomics revealed that 33 and 9 proteins were significantly upregulated and downregulated, respectively, in L. lactis N8-1. These differential proteins were involved in carbohydrate and energy transport/metabolism, biosynthesis of cell wall and cell surface proteins.

Conclusions

PRF deletion was proven to be an efficient strategy to achieve multi-stress tolerance and nisin immunity in L. lactis, thereby providing a new perspective for industrially obtaining engineered strains with multi-stress tolerance and expanding the application of lactic acid bacteria in biotechnology and synthetic biology. Besides, the importance of PRF, which can confer vital phenotypes to bacteria, was established.
MAFG-AS1 aggravates the progression of pancreatic cancer by sponging miR-3196 to boost NFIX
Authors: Ye Liqing , Feng Weijian , Weng Hanqin , Yuan Chongde , Liu Jia , Wang Zaiguo
Published: December 2020

Background

A host of researches have demonstrated the regulation of long non-coding RNAs (lncRNAs) in the progression of pancreatic cancers (PC). In this study, our main task was to analyze the function of MAF bZIP transcription factor G antisense RNA 1 (MAFG-AS1) in PC.

Methods

RT-qPCR measured gene expression. Functional experiments, including EdU assay, flow cytometry analysis, TUNEL assay and transwell assay, assessed the biological changes of PC cells. RNA pull down assay, luciferase reporter assay and RIP assay verified the interaction between RNAs.

Results

MAFG-AS1 was lowly expressed in normal pancreatic samples but up-regulated in PC tissues and cell lines. Besides, MAFG-AS1 silence suppressed cell proliferation and migration whereas promoted cell apoptosis in PC. Mechanism assays verified that miR-3196 could bind with MAFG-AS1. Moreover, miR-3196 was discovered to be lowly expressed in PC cell lines, and its overexpression inhibited PC cell growth and migration. Importantly, nuclear factor I X (NFIX), overexpressed in PC cell lines, was validated to be positively modulated by MAFG-AS1 through absorbing miR-3196. Moreover, overexpression of NFIX could countervail the restraining effects of MAFG-AS1 knockdown on the growth and migration of PC cells.

Conclusion

MAFG-AS1 had an oncogenic function in the progression of PC via regulating miR-3196/NFIX pathway, and decreasing MAFG-AS1 expression could attenuate PC progression.
The interplay between ATF2 and NEAT1 contributes to lung adenocarcinoma progression
Authors: Liu Jian , Li Kai , Wang Rui , Chen Sisi , Wu Jie , Li Xiang , Ning Qian , Yang Ganghua , Pang Yamei
Published: December 2020

Background

Activating transcription factor 2 (ATF2), a member of the activator protein 1 (AP-1) transcription factor family, has been shown to be involved in the pathobiology of numerous cancers. However, the biological role and mechanism of ATF2 in lung adenocarcinoma (LUAD) remains to be elucidated.

Methods

The expression of ATF2, NEAT1 and miR-26a-5p in LUAD tissues and cell lines was detected by qRT-PCR and western blotting. The interaction between ATF2, NEAT1, and miR-26a-5p was validated by chromatin immunoprecipitation, luciferase reporter assay and RNA immunoprecipitation. Cell proliferation, invasion and tumorigenesis of LUAD cells were analyzed by using CCK8, transwell invasion assay and xenograft tumor model.

Results

We confirmed that ATF2 expression was increased in LUAD tissues compared with normal adjacent lung tissues. Functional experiments showed that ATF2 positively regulated cell proliferation and invasion in LUAD cells. Moreover, we identified that NEAT1 expression was increased in LUAD tissues and positively correlated with ATF2 expression. Mechanistically, ATF2 could bind to the promoter of NEAT1 to promote its transcription. Rescue experiments showed that ATF2 exerted its oncogenic function in LUAD, at least, partly through NEAT1 upregulation. In turn, NEAT1 could positively regulate ATF2 expression and form a positive feedback loop in LUAD cells. Furthermore, we demonstrated that NEAT1 positively regulated ATF2 expression via sponging miR-26a-5p.

Conclusion

ATF2 and NEAT1 form a positive feedback loop mediated by miR-26a-5p and coordinately contribute to LUAD progression.
Social exclusion and universal health coverage: health care rights and citizen-led accountability in Guatemala and Peru
Authors: Samuel Jeannie , Flores Walter , Frisancho Ariel
Published: December 2020

Background

While equity is a central concern in promoting Universal Health Coverage (UHC), the impact of social exclusion on equity in UHC remains underexplored. This paper examines challenges faced by socially excluded populations, with an emphasis on Indigenous peoples, to receive UHC in Latin America. We argue that social exclusion can have negative effects on health systems and can undermine progress towards UHC. We examine two case studies, one in Guatemala and one in Peru, involving citizen-led accountability initiatives that aim to identify and address problems with health care services for socially excluded groups. The case studies reveal how social exclusion can affect equity in UHC.

Methods

In-depth analysis was conducted of all peer reviewed articles published between 2015 and 2019 on the two cases (11 in total), and two non-peer reviewed reports published over the same period. In addition, two of the three authors contributed their first-hand knowledge gathered through practitioner involvement with the citizen-led initiatives examined in the two cases. The analysis sought to identify and compare challenges faced by socially excluded Indigenous populations to receive UHC in the two cases.

Results

Citizen-led accountability initiatives in Guatemala and Peru reveal very similar patterns of serious deficiencies that undermine efforts towards the realization of Universal Health Coverage in both countries. In each case, the socially excluded populations are served by a dysfunctional publicly provided health system marked by gaps and often invisible barriers. The cases suggest that, while funding and social rights to coverage have expanded, marginalized populations in Guatemala and Peru still do not receive either the health care services or the protection against financial hardship promised by health systems in each country. In both cases, the dysfunctional character of the system remains in place, undermining progress towards UHC.

Conclusions

We conclude that efforts to promote UHC cannot stop at increasing health systems financing. In addition, these efforts need to contend with the deeper challenges of democratizing state institutions, including health systems, involved in marginalizing and excluding certain population groups. This includes stronger accountability systems within public institutions. More inclusive accountability mechanisms are an important step in promoting equitable progress towards UHC.
Evaluation of Rapid Sepsityper® protocol and specific MBT-Sepsityper module (Bruker Daltonics) for the rapid diagnosis of bacteremia and fungemia by MALDI-TOF-MS
Authors: Ponderand Léa , Pavese Patricia , Maubon Danièle , Giraudon Emmanuelle , Girard Thomas , Landelle Caroline , Maurin Max , Caspar Yvan
Published: December 2020

During bloodstream infections, rapid adaptation of empirical treatment according to the microorganism identified is essential to decrease mortality. The aim of the present study was to assess the microbiological performances of a new rapid version of the Sepsityper® kit (Bruker Daltonics) allowing identification of bacteria and yeast by MALDI-TOF mass spectrometry directly from positive blood cultures in 10 min and of the specific MBT-Sepsityper module for spectra analysis, designed to increase identification performance. Identification rates were determined prospectively on 350 bacterial and 29 fungal positive blood cultures, and compared to conventional diagnostic method. Our rapid diagnosis strategy (Rapid Sepsityper® protocol: one spot with and one without formic acid extraction step) combined to MBT-Sepsityper module provided 65.4%, 78.9% and 62% reliable identification to the species level of monomicrobial positive blood cultures growing respectively Gram-positive, Gram-negative bacteria or yeast. Importantly, identification rates of Gram-positive bacteria were higher in anaerobic than in aerobic bottles (77.8% vs 22.2%; p = 0.004), if formic acid extraction step was performed (60.8% vs 39.2%; p = 1.8e−6) and if specific MBT-Sepsityper module was used (76.2% vs 61.9%, p = 0.041) while no significant differences were observed for Gram-negative bacteria. For yeasts identification, formic acid extraction step improved rapid identification rate by 37.9% while the specific MBT-Sepsityper module increased overall performances by 38%, providing up to 89.7% reliable identification if associated with the standard Sepsityper® protocol. These performances, associated with a reduce turnaround time, may help to implement a rapid identification strategy of bloodstream infections in the routine workflow of microbiology laboratories.
An ethical analysis of UK drug policy as an example of a criminal justice approach to drugs: a commentary on the short film Putting UK Drug Policy into Focus
Authors: Holland Adam
Published: December 2020

Background

Drug-related deaths in the UK are at the highest level on record—the war on drugs has failed. A short film has been produced intended for public and professional audiences featuring academics, representatives of advocacy organisations, police and policymakers outlining the problems with, and highlighting alternative approaches to, UK drug policy. A range of ethical arguments are alluded to, which are distilled here in greater depth for interested viewers and a wider professional and academic readership.

Main body

The war on drugs is seemingly driven by the idea that the consumption of illegal drugs is immoral. However, the meaning ascribed to ‘drug’ in the illicit sense encompasses a vast range of substances with different properties that have as much in common with legal drugs as they do with each other. The only property that distinguishes illegal from legal drugs is their legal status, which rather than being based on an assessment of how dangerous they are has been defined by centuries of socio-political idiosyncrasies. The consequences of criminalising people who use drugs often outweigh the risks they face from drug use, and there is not convincing evidence that this prevents wider drug use or drug-related harm. Additionally, punishing someone as a means, to the end of deterring others from drug use, is ethically problematic. Although criminalising the production of harmful drugs may seem more ethically tenable, it has not reduced the supply of drugs and it precludes effective regulation of the market. Other potential policy approaches are highlighted, which would be ethically preferable to existing punitive policy.

Conclusion

It is not possible to eliminate all drug use and associated harms. The current approach is not only ineffective in preventing drug-related harm but itself directly and indirectly causes incalculable harm to those who use drugs and to wider society. For policymakers to gain the mandate to rationalise drug policy, or to be held accountable if they do not, wider engagement with the electorate is required. It is hoped that this film will encourage at least a few to give pause and reflect on how drug policy might be improved.
Modified reverse-puncture anastomotic technique vs. traditional technique for total minimally invasive Ivor-Lewis esophagectomy
Authors: Shen Xiaokang , Chen Tianming , Shi Xiaoming , Zheng Ming , Zhou Zhang Yan , Qiu Hai Tao , Zhao Jiawei , Lu Peng , Yang Po , Chen Shilin
Published: December 2020

Background

Total endoscopic Ivor-Lewis esophagectomy is a challenging, complex, and costly operation. These disadvantages restrict its wide application. The aim of this study was to compare the modified reverse-puncture anastomotic technique and traditional technique for total minimally invasive Ivor-Lewis esophagectomy.

Methods

In this cohort retrospective study, all patients with medial and lower squamous cell carcinoma of esophagus from February 2014 and June 2018 were divided into two groups according to the surgical method, which were modified reverse-puncture anastomotic technique group and traditional technique group. The operation time, intraoperative bleeding volume, complications, and cost of the two groups were compared.

Results

Forty-eight patients in the modified reverse-puncture anastomotic technique group while 54 patients in the traditional technique group were included. The operation time was 293.4 ± 57.2 min in the modified reverse-puncture anastomotic technique group, which was significantly shorter than that in the traditional technique group (353.4 ± 64.1 min) (P < 0.05). The intraoperative bleeding volume of modified reverse-puncture anastomotic technique group was 157.3 ± 107.4 ml, while it was 191.9 ± 123.6 ml in traditional technique group (P = 0.14). There were similar complications between the two groups. The cost of modified reverse-puncture anastomotic and traditional technique in our hospital were and 72 ± 13 and 83 ± 41 thousand Yuan, respectively (P = 0.08).

Conclusion

The good short-term outcomes that were achieved suggested that the use of modified reverse-puncture anastomotic technique is safe and feasible for total endoscopic Ivor-Lewis esophagectomy.
Precision medicine in the era of artificial intelligence: implications in chronic disease management
Authors: Subramanian Murugan , Wojtusciszyn Anne , Favre Lucie , Boughorbel Sabri , Shan Jingxuan , Letaief Khaled B. , Pitteloud Nelly , Chouchane Lotfi
Published: December 2020

Aberrant metabolism is the root cause of several serious health issues, creating a huge burden to health and leading to diminished life expectancy. A dysregulated metabolism induces the secretion of several molecules which in turn trigger the inflammatory pathway. Inflammation is the natural reaction of the immune system to a variety of stimuli, such as pathogens, damaged cells, and harmful substances. Metabolically triggered inflammation, also called metaflammation or low-grade chronic inflammation, is the consequence of a synergic interaction between the host and the exposome—a combination of environmental drivers, including diet, lifestyle, pollutants and other factors throughout the life span of an individual. Various levels of chronic inflammation are associated with several lifestyle-related diseases such as diabetes, obesity, metabolic associated fatty liver disease (MAFLD), cancers, cardiovascular disorders (CVDs), autoimmune diseases, and chronic lung diseases. Chronic diseases are a growing concern worldwide, placing a heavy burden on individuals, families, governments, and health-care systems. New strategies are needed to empower communities worldwide to prevent and treat these diseases. Precision medicine provides a model for the next generation of lifestyle modification. This will capitalize on the dynamic interaction between an individual’s biology, lifestyle, behavior, and environment. The aim of precision medicine is to design and improve diagnosis, therapeutics and prognostication through the use of large complex datasets that incorporate individual gene, function, and environmental variations. The implementation of high-performance computing (HPC) and artificial intelligence (AI) can predict risks with greater accuracy based on available multidimensional clinical and biological datasets. AI-powered precision medicine provides clinicians with an opportunity to specifically tailor early interventions to each individual. In this article, we discuss the strengths and limitations of existing and evolving recent, data-driven technologies, such as AI, in preventing, treating and reversing lifestyle-related diseases.
A kinematic posture analysis of neurological assistants in their daily working practice-a pilot study
Authors: Bijanzadeh Anne , Hermanns Ingo , Ellegast Rolf , Fraeulin Laura , Holzgreve Fabian , Mache Stefanie , Groneberg David A. , Ohlendorf Daniela
Published: December 2020

Background

The aim of this pilot study was to analyze postures during the work of neurologists with respect to their occupational activities.

Methods

A total data material of 64.8 h (3885.74 min) of nine (three m/six f) neurologists (assistant physicians) was collected. Kinematic data were collected using the CUELA system (electro-goniometry). In addition, the occupational tasks performed on-site were subject to a detailed objective activity analysis. All activities were assigned to the categories “Office activities” (I), “Measures on patients” (II) and “Other activities” (III). The angle values of each body region (evaluation parameters) were evaluated according to ergonomic ISO standards.

Results

Only 3.4% of the working hours were spent with (II), while 50.8% of time was spent with (I) and 45.8% with (III). All tasks of category (II) revealed an increased ergonomic risk to the head, neck, trunk and back areas. During category (I) especially neck and back movements in the sagittal plane showed higher ergonomic risk levels.

Conclusion

Despite frequently performed awkward body positions in (II), the ergonomic risk is considered as rather low, since the percentage time share totaled only 3.4%. As a result, “Office activities” have been detected as high predictor to cause stress load on the musculoskeletal system in the daily work of neurologists.
Hyperplastic polyp or sessile serrated lesion? The contribution of serial sections to reclassification
Authors: Jaravaza Diana R. , Rigby Jonathan M.
Published: December 2020

Background

The histological discrimination of hyperplastic polyps from sessile serrated lesions can be difficult. Sessile serrated lesions and hyperplastic polyps are types of serrated polyps which confer different malignancy risks, and surveillance intervals, and are sometimes difficult to discriminate. Our aim was to reclassify previously diagnosed hyperplastic polyps as sessile serrated lesions or confirmed hyperplastic polyps, using additional serial sections.

Methods

Clinicopathological data for all colorectal hyperplastic polyps diagnosed in 2016 and 2017 was collected. The slides were reviewed and classified as hyperplastic polyps, sessile serrated lesion, or other, using current World Health Organization criteria. Eight additional serial sections were performed for the confirmed hyperplastic polyp group and reviewed.

Results

Of an initial 147 hyperplastic polyps from 93 patients, 9 (6.1%) were classified as sessile serrated lesions, 103 as hyperplastic polyps, and 35 as other. Of the 103 confirmed hyperplastic polyps, 7 (6.8%) were proximal, and 8 (7.8%) had a largest fragment size of ≥5 mm and < 10 mm. After 8 additional serial sections, 11 (10.7%) were reclassified as sessile serrated lesions. They were all less than 5 mm and represented 14.3% of proximal polyps and 10.4% of distal polyps. An average of 3.6 serial sections were required for a change in diagnosis.

Conclusion

Histopathological distinction between hyperplastic polyps and sessile serrated lesions remains a challenge. This study has uncovered a potential role for the use of additional serial sections in the morphological reappraisal of small hyperplastic polyps, especially when proximally located.
Barriers and facilitators of implementation of a community cardiovascular disease prevention programme in Mukono and Buikwe districts in Uganda using the Consolidated Framework for Implementation Research
Authors: Ndejjo Rawlance , Wanyenze Rhoda K. , Nuwaha Fred , Bastiaens Hilde , Musinguzi Geofrey
Published: December 2020

Background

In low- and middle-income countries, there is an increasing attention towards community approaches to deal with the growing burden of cardiovascular disease (CVD). However, few studies have explored the implementation processes of such interventions to inform their scale up and sustainability. Using the consolidated framework for implementation research (CFIR), we examined the barriers and facilitators influencing the implementation of a community CVD programme led by community health workers (CHWs) in Mukono and Buikwe districts in Uganda.

Methods

This qualitative study is a process evaluation of an ongoing type II hybrid stepped wedge cluster trial guided by the CFIR. Data for this analysis were collected through regular meetings and focus group discussions (FGDs) conducted during the first cycle (6 months) of intervention implementation. A total of 20 CHWs participated in the implementation programme in 20 villages during the first cycle. Meeting reports and FGD transcripts were analysed following inductive thematic analysis with the aid of Nvivo 12.6 to generate emerging themes and sub-themes and thereafter deductive analysis was used to map themes and sub-themes onto the CFIR domains and constructs.

Results

The barriers to intervention implementation were the complexity of the intervention (complexity), compatibility with community culture (culture), the lack of an enabling environment for behaviour change (patient needs and resources) and mistrust of CHWs by community members (relative priority). In addition, the low community awareness of CVD (tension for change), competing demands (other personal attributes) and unfavourable policies (external policy and incentives) impeded intervention implementation. On the other hand, facilitators of intervention implementation were availability of inputs and protective equipment (design quality and packaging), training of CHWs (Available resources), working with community structures including leaders and groups (process—opinion leaders), frequent support supervision and engagements (process—formally appointed internal implementation leaders) and access to quality health services (process—champions).

Conclusion

Using the CFIR, we identified drivers of implementation success or failure for a community CVD prevention programme in a low-income context. These findings are key to inform the design of impactful, scalable and sustainable CHW programmes for non-communicable diseases prevention and control.
Stereotactic radiosurgery of benign brain tumors in elderly patients: evaluation of outcome and toxicity
Authors: Rueß Daniel , Weyer Vera , Tutunji Juman , Grau Stefan , Kocher Martin , Hoevels Mauritius , Treuer Harald , Baues Christian , Ruge Maximilian I.
Published: December 2020

Background

Stereotactic radiosurgery (SRS) is widely accepted as a therapeutic option for meningiomas (M) and vestibular schwannomas (VS). However, data on outcome and toxicity in the elderly population have rarely been reported in detail.

Methods

All patients aged ≥ 65 years with M or VS who underwent single fraction SRS were included. Patient data were analyzed in terms of clinical tumor control and incidence of early and late treatment related complications, which were graded according to the Common Terminology Criteria for Adverse Events (CTCAE),

Results

We identified 245 patients with benign brain tumors (129 M and 116 VS, median tumor volume 2.9 ml, range 0.1–28). The median age was 71 years (range 65–86) and the mean follow-up times were 42 months (range 2–181). Tumors were irradiated with a median dose of 12.4 Gy. Actuarial clinical and radiological tumor control rates at 2, 5, and 10 years after SRS were 98%, 93%, and 88%, respectively. Recurrent tumors after previous treatment had a higher probability of post-radiosurgical progression (p < 0.001). Permanent toxicity (CTCAE I/II) were noted in 5.7%. No severe adverse events were observed during early and late follow up, although patients > 70 years had a slightly higher risk for toxicity (p = 0.027). The presence and extent of co-morbidities had no significant influence on local tumor control or toxicity.

Conclusion

SRS provides favorable tumor control with low risk for treatment-related severe complications. Thus, SRS should always be considered as treatment option for benign intracranial tumors (meningiomas, schwannomas), especially in the group of elderly patients.
Long-term outcome of stereotactic brachytherapy with temporary Iodine-125 seeds in patients with WHO grade II gliomas
Authors: Watson Juliana , Romagna Alexander , Ballhausen Hendrik , Niyazi Maximilian , Lietke Stefanie , Siller Sebastian , Belka Claus , Thon Niklas , Nachbichler Silke Birgit
Published: December 2020

Background

This long-term retrospective analysis aimed to investigate the outcome and toxicity profile of stereotactic brachytherapy (SBT) in selected low-grade gliomas WHO grade II (LGGII) in a large patient series.

Methods

This analysis comprised 106 consecutive patients who received SBT with temporary Iodine-125 seeds for histologically verified LGGII at the University of Munich between March 1997 and July 2011. Investigation included clinical characteristics, technical aspects of SBT, the application of other treatments, outcome analyses including malignization rates, and prognostic factors with special focus on molecular biomarkers.

Results

For the entire study population, the 5- and 10-years overall survival (OS) rates were 79% and 62%, respectively, with a median follow-up of 115.9 months. No prognostic factors could be identified. Interstitial radiotherapy was applied in 51 cases as first-line treatment with a median number of two seeds (range 1–5), and a median total implanted activity of 21.8 mCi (range 4.2–43.4). The reference dose average was 54.0 Gy. Five- and ten-years OS and progression-free survival rates after SBT were 72% and 43%, and 40% and 23%, respectively, with a median follow-up of 86.7 months. The procedure-related mortality rate was zero, although an overall complication rate of 16% was registered. Patients with complications had a significantly larger tumor volume (p = 0.029).

Conclusion

SBT is a minimally invasive treatment modality with a favorable outcome and toxicity profile. It is both an alternative primary treatment method as well as an adjunct to open tumor resection in selected low-grade gliomas.
Impact of the SARS-CoV-2 pandemic on emergency surgery services—a multi-national survey among WSES members
Authors:   The WSES COVID-19 emergency surgery survey collaboration group, Reichert Martin , Sartelli Massimo , Weigand Markus A. , Doppstadt Christoph , Hecker Matthias , Reinisch-Liese Alexander , Bender Fabienne , Askevold Ingolf , Padberg Winfried , Coccolini Federico , Catena Fausto , Hecker Andreas
Published: December 2020

Background

The SARS-CoV-2 pandemic is a major challenge for health care services worldwide. It’s impact on oncologic therapies and elective surgery has been described recently, and the literature provides guidelines regarding appropriate elective patient treatment during the pandemic. However, the impact of SARS-CoV-2 pandemic on emergency surgery services has been poorly investigated up to now.

Methods

A 17-item web survey had been distributed to emergency surgeons in June 2020 around the world, investigating the impact of SARS-CoV-2 pandemic on patients and septic diseases both requiring emergency surgery and the time-to-intervention in emergency surgery routine, as well as experiences with surgery in COVID-19 patients.

Results

Ninety-eight collaborators from 31 countries responded to the survey. The majority (65.3%) estimated the impact of the SARS-CoV-2 pandemic on emergency surgical patient care as being strong or very strong. Due to the pandemic, 87.8% reported a decrease in the total number of patients undergoing emergency surgery and approximately 25% estimated a delay of more than 2 h in the time-to-diagnosis and another 2 h in the time-to-intervention. Fifty percent make structural problems with in-hospital logistics (e.g. transport of patients, closed normal wards etc.) mainly responsible for delayed emergency surgery and the frequent need (56.1%) for a triage of emergency surgical patients. 56.1% of the collaborators observed more severe septic abdominal diseases during the pandemic, especially for perforated appendicitis and severe septic cholecystitis (41.8% and 40.2%, respectively). 62.2% had experiences with surgery in COVID-19-infected patients.

Conclusions

The results of The WSES COVID-19 emergency surgery survey are alarming. The combination of an estimated decrease in numbers of emergency surgical patients and an observed increase in more severe septic diseases may be a result of the fear of patients from infection with COVID-19 and a consecutive delayed hospital admission and diagnosis. A critical delay in time-to-diagnosis and time-to-intervention may be a result of changes in in-hospital logistics and operating room as well as intensive care capacities. Both reflect the potentially harmful impact of SARS-CoV-2 pandemic on emergency surgery services.
Clinical value of CT-based patient-specific 3D preoperative design combined with conventional instruments in primary total knee arthroplasty: a propensity score-matched analysis
Authors: Lei Kai , Liu Li Ming , Xiang Yi , Chen Xin , Fan Hua Quan , Peng Yang , Luo Jiang Ming , Guo Lin
Published: December 2020

Purpose

To evaluate the operation and early clinical effect in primary total knee arthroplasty (TKA) about the novel combination of CT-based patient-specific three-dimensional (3D) preoperative design and conventional osteotomy instruments, compared with the conventional method.

Methods

After a 1:1 propensity score-matching (PSM), patients were matched to the novel technique group and the conventional group, 109 cases in each group. The conventional group adopted a preoperative design based on a full-length radiograph (FLX) and received TKA with conventional osteotomy instruments. The novel technique group used a CT-based patient-specific 3D preoperative design combined with conventional osteotomy instruments; during the surgery, the femoral entry point, femoral valgus osteotomy angle, the fix point of tibial plateau extramedullary guide pin, and the position of tibial extramedullary positioning rod were accurately selected according to the preoperative 3D design to ensure accurate intraoperative implementation. The lower limb alignment, component position, operation time, tourniquet time, hospital stay, blood loss volume, incidence of postoperative complications, visual analog scale (Vas) score, and New Knee Society Score System (NEW-KSS) at 1 day before operation and 1, 6, and 12 months after operation were recorded and compared.

Results

The novel technique group was significantly better than the conventional group in controlling lateral tibial component angle (LTC) (P< 0.001), and the novel technique group had lower percentages of hip-knee-ankle angle (HKA) outliers (P< 0.001) and overcorrection (P= 0.003). The operation time, tourniquet time, and hospital stay of the novel technique group was shorter (P< 0.05). In 1 month after the operation, the novel technique group achieved a significantly better VAS score (P< 0.05), but a similar NEW-KSS score (P> 0.05) when compared with the conventional group. But in 6 and 12 months after surgery, no statistical differences were seen in the above two scores (P> 0.05).

Conclusion

The novel technique of CT-based patient-specific 3D preoperative design combined with conventional instruments can improve the accuracy of osteotomy in primary total knee arthroplasty, with benefits of significantly reducing pain and rapid recovery during the early postoperative period, but having no obvious effect on outcome after a 1-year follow-up.
Gradual ulnar lengthening in Masada type I/IIb deformity in patients with hereditary multiple osteochondromas: a retrospective study with a mean follow-up of 4.2 years
Authors: Li Yuchan , Wang Zhigang , Chen Mu , Cai Haoqi
Published: December 2020

Background

Gradual ulnar lengthening is the most commonly used procedure in the treatment of Masada type I/II deformity in patients with hereditary multiple osteochondromas. However, the treatment remains controversial for the recurrence of deformity in growing children. This study aims to evaluate the clinical and radiological outcomes of ulnar gradual lengthening in our clinic.

Methods

We retrospectively reviewed patients who underwent ulnar lengthening by distraction osteogenesis from June 2008 to October 2017. The carrying angle (CA) and range of motion (ROM) of the forearm and elbow were clinically assessed, and the radial articular angle (RAA) and ulnar shortening (US) were radiologically assessed before lengthening, 2 months after external frame removal, and at the last follow-up.

Results

The current study included 15 patients (17 forearms) with a mean age of 9.4 ± 2.3 years at the index surgery. The mean follow-up period was 4.2 ± 2.4 years. There were 9 patients (10 forearms) with Masada type I deformity and 6 patients (7 forearms) with Masada type IIb deformity. The mean amount of ulnar lengthening was 4.2 ± 1.2 cm. The mean RAA improved from 37 ± 8 to 30 ± 7° initially (p = 0.005) and relapsed to 34 ± 8° at the last follow-up (p = 0.255). There was a minimal deterioration of US yet significant improvement at the last follow-up compared to pre-op (p < 0.001). At the last follow-up, the mean forearm pronation and elbow flexion increased significantly (p < 0.001 and p = 0.013, respectively), and the mean carrying angle also improved significantly (p < 0.001). No patient with type IIb deformity achieved a concentric radial head reduction.

Conclusions

Gradual ulnar lengthening significantly reduces cosmetic deformity and improves function in patients with Masada type I/IIb deformity. Our results supported early ulnar lengthening for patients with a tendency of dislocation of the radial head.
The drug likeness analysis of anti-inflammatory clerodane diterpenoids
Authors: Feng Zheling , Cao Jun , Zhang Qingwen , Lin Ligen
Published: December 2020

Inflammation is an active defense response of the body against external stimuli. Long term low-grade inflammation has been considered as a deteriorated factor for aging, cancer, neurodegeneration and metabolic disorders. The clinically used glucocorticoids and non-steroidal anti-inflammatory drugs are not suitable for chronic inflammation. Therefore, it’s urgent to discover and develop new effective and safe drugs to attenuate inflammation. Clerodane diterpenoids, a class of bicyclic diterpenoids, are widely distributed in plants of the Labiatae, Euphorbiaceae and Verbenaceae families, as well as fungi, bacteria, and marine sponges. Dozens of anti-inflammatory clerodane diterpenoids have been identified on different assays, both in vitro and in vivo. In the current review, the up-to-date research progresses of anti-inflammatory clerodane diterpenoids were summarized, and their druglikeness was analyzed, which provided the possibility for further development of anti-inflammatory drugs.
Root causes of elective surgical case cancellation in Ethiopia: a systematic review and meta-analysis
Authors: Birhanu Yeneabat , Endalamaw Aklilu , Adu Aynalem
Published: December 2020

Background

Cancellation of elective surgical operation recognized as a major cause of emotional trauma to patients as well as their families. In Ethiopia, prevalence and root causes for elective surgical case cancellation varies from time to time in different settings. This systematic review and meta-analysis aimed to find the pooled prevalence and root causes for elective surgical case cancellation in Ethiopia.

Methods

The databases for the search were Web of Science, PubMed, and Google Scholar. The last literature search was performed on February 8, 2020. To assess publication bias Egger’s regression analysis was applied. The pooled estimation was estimated using random-effects model meta-analysis. Subgroup analysis was also done based on the root causes of surgical case cancellation.

Results

This meta-analysis included a total of 5 studies with 5591 study participants. The pooled prevalence of elective surgical case cancellation was 21.41% (95% CI: 12.75 to 30.06%).

Administration-related reason (34.50%) was the most common identified root cause, followed by surgeon (25.29%), medical (13.90%), and patient-related reasons (13.34%).

Conclusion

The prevalence of elective surgical case cancellation was considerable. The most common root cause for elective surgical case cancellation was administration-related reasons, followed by the surgeon, medical and patient-related reasons. The causes for the surgical cancellations are potentially preventable. Thus, efforts should be made to prevent unnecessary cancellations through careful planning.
Chidamide increases the sensitivity of refractory or relapsed acute myeloid leukemia cells to anthracyclines via regulation of the HDAC3 -AKT-P21-CDK2 signaling pathway
Authors: Wang Hao , Liu Yu-chen , Zhu Cheng-ying , Yan Fei , Wang Meng-zhen , Chen Xiao-su , Wang Xiao-kai , Pang Bao-xu , Li Yong-hui , Liu Dai-hong , Gao Chun-ji , Liu Shu-jun , Dou Li-ping
Published: December 2020

Background

Induction therapy for acute myeloid leukemia (AML) is an anthracycline-based chemotherapy regimen. However, many patients experience a relapse or exhibit refractory disease (R/R). There is an urgent need for more effective regimens to reverse anthracycline resistance in these patients.

Methods

In this paper, Twenty-seven R/R AML patients with anthracycline resistance consecutively received chidamide in combination with anthracycline-based regimen as salvage therapy at the Chinese PLA General Hospital.

Results

Of the 27 patients who had received one course of salvage therapy, 13 achieved a complete response and 1 achieved a partial response. We found that the HDAC3-AKT-P21-CDK2 signaling pathway was significantly upregulated in anthracycline-resistant AML cells compared to non-resistant cells. AML patients with higher levels of HDAC3 had lower event-free survival (EFS) and overall survival (OS) rates. Moreover, anthracycline-resistant AML cells are susceptible to chidamide, a histone deacetylase inhibitor which can inhibit cell proliferation, increase cell apoptosis and induce cell-cycle arrest in a time- and dose-dependent manner. Chidamide increases the sensitivity of anthracycline-resistant cells to anthracycline drugs, and these effects are associated with the inhibition of the HDAC3-AKT-P21-CDK2 signaling pathway.

Conclusion

Chidamide can increase anthracycline drug sensitivity by inhibiting HDAC3-AKT-P21-CDK2 signaling pathway, thus demonstrating the potential for application.
Cathepsin V suppresses GATA3 protein expression in luminal A breast cancer
Authors: Sereesongsaeng Naphannop , McDowell Sara H. , Burrows James F. , Scott Christopher J. , Burden Roberta E.
Published: December 2020

Background

Lysosomal cysteine protease cathepsin V has previously been shown to exhibit elevated expression in breast cancer tissue and be associated with distant metastasis. Research has also identified that cathepsin V expression is elevated in tumour tissues from numerous other malignancies, but despite this, there has been limited examination of the function of this protease in cancer. Here we investigate the role of cathepsin V in breast cancer in order to delineate the molecular mechanisms by which this protease contributes to tumourigenesis.

Methods

Lentiviral transductions were used to generate shRNA cell line models, with cell line validation undertaken using RQ-PCR and Western blotting. Phenotypic changes of tumour cell biology were examined using clonogenic and invasion assays. The relationship between GATA3 expression and cathepsin V was primarily analysed using Western blotting. Site-directed mutagenesis was used to generate catalytic mutant and shRNA-resistant constructs to confirm the role of cathepsin V in regulating GATA3 expression.

Results

We have identified that elevated cathepsin V expression is associated with reduced survival in ER-positive breast cancers. Cathepsin V regulates the expression of GATA3 in ER-positive breast cancers, through promoting its degradation via the proteasome. We have determined that depletion of cathepsin V results in elevated pAkt-1 and reduced GSK-3β expression, which rescues GATA3 from proteasomal degradation.

Conclusions

In this study, we have identified that cysteine protease cathepsin V can suppress GATA3 expression in ER-positive breast cancers by facilitating its turnover via the proteasome. Therefore, targeting cathepsin V may represent a potential therapeutic strategy in ER-positive breast cancers, by restoring GATA3 protein expression, which is associated with a more favourable clinical outcome.
Effects of football versus aerobic exercise training on muscle architecture in healthy men adults: a study protocol of a two-armed randomized controlled trial
Authors: Alkhateeb Guevar , Donath Lars
Published: December 2020

Background

Sports and exercise training can attenuate age-related declines in physical function. As people age, they suffer a progressive deterioration of overall muscle structure and function, such as muscle diameter, strength, mass, and power. Therefore, supporting older adults—aged 50 years and above—to continue being physically active is a very important factor. Several forms of exercise (strength, agility, endurance, balance, and flexibility) are recommended. In this regard, football has been repeatedly shown to be an integrative approach to promote measures of strength, endurance, and agility. However, there has been no previous randomized controlled trial that comparatively investigates the effects of football training versus traditional aerobic exercise training on muscle architecture and patella tendon properties in healthy community dwellers. The study protocol is designed to examine whether football differentially affects muscle thickness, muscle length, fascicle length, pennation angle, patella tendon length, and thickness compared to a workload matched traditional aerobic exercise training regimen.

Methods

The study sample consists of 60 untrained but healthy men (50–60 years old), who will be randomly assigned (strata: age, activate) to two groups: football group (n = 30) and aerobic group (n = 30). The intervention will take place within 12 consecutive weeks, two times a week for 60 min each session. The football group will perform recreational football training as a large-sided game, whereas the aerobic group undergoes a running exercise. Both groups have the same external workload ranging between moderate and high exercise intensity. The outcome measure will be collected before and after the intervention period.

Discussion

Findings of this study will provide insight into the effects of 24 sessions of both football and aerobic training program on the selected groups of men adults, including detecting their effects on the thigh muscle architecture.

Trial registration

DRKS—German Clinical Trials Register, DRKS00020536. Registered on 30 January 2020.