bluuebunny/crossref_metadata_2025_split huggingface dataset:
A versatile contribution of both aminopeptidases N and ABC transporters to Bt Cry1Ac toxicity in the diamondback moth
Authors: Sun Dan , Zhu Liuhong , Guo Le , Wang Shaoli , Wu Qingjun , Crickmore Neil , Zhou Xuguo , Bravo Alejandra , Soberón Mario , Guo Zhaojiang , Zhang Youjun 
Published: February 2022

Abstract
Background
Biopesticides and transgenic crops based on Bacillus thuringiensis (Bt) toxins are extensively used to control insect pests, but the rapid evolution of insect resistance seriously threatens their effectiveness. Bt resistance is often polygenic and complex. Mutations that confer resistance occur in midgut proteins that act as cell surface receptors for the toxin, and it is thought they facilitate its assembly as a membrane-damaging pore. However, the mechanistic details of the action of Bt toxins remain controversial.

Results
We have examined the contribution of two paralogous ABC transporters and two aminopeptidases N to Bt Cry1Ac toxicity in the diamondback moth, Plutella xylostella, using CRISPR/Cas9 to generate a series of homozygous polygenic knockout strains. A double-gene knockout strain, in which the two paralogous ABC transporters ABCC2 and ABCC3 were deleted, exhibited 4482-fold resistance to Cry1A toxin, significantly greater than that previously reported for single-gene knockouts and confirming the mutual functional redundancy of these ABC transporters in acting as toxin receptors in P. xylostella. A double-gene knockout strain in which APN1 and APN3a were deleted exhibited 1425-fold resistance to Cry1Ac toxin, providing the most direct evidence to date for these APN proteins acting as Cry1Ac toxin receptors, while also indicating their functional redundancy. Genetic crosses of the two double-gene knockouts yielded a hybrid strain in which all four receptor genes were deleted and this resulted in a > 34,000-fold resistance, indicating that while both types of receptor need to be present for the toxin to be fully effective, there is a level of functional redundancy between them. The highly resistant quadruple knockout strain was less fit than wild-type moths, but no fitness cost was detected in the double knockout strains.

Conclusion
Our results provide direct evidence that APN1 and APN3a are important for Cry1Ac toxicity. They support our overarching hypothesis of a versatile mode of action of Bt toxins, which can compensate for the absence of individual receptors, and are consistent with an interplay among diverse midgut receptors in the toxins’ mechanism of action in a super pest.
Isolated complete caudate lobectomy with Glissonean pedicle isolation using Takasaki’s technique and right–left approach: preliminary experience from two case reports
Authors: Nguyen Ham Hoi , Nguyen Thanh Khiem , Le Van Duy , Luong Tuan Hiep , Dang Kim Khue , Nguyen Vu Quang , Trinh Hong Son 
Published: February 2022

Abstract
Background
Tumors located in the caudate lobe may be primary tumor or metastases from other sites. Isolated caudate lobectomy (ICL) is a challenging procedure due to its complex structure and location. The access route to the caudate lobe has an important role in the success of the operation.

Methods
Based on the characteristics of the segment I location, which is the part of the liver located in front of the vena cava, below the hepatic veins, and cranial to the hilar plate, our approach aims to isolate the entire caudate lobe from these anatomical structures with the following steps: dissecting the caudate lobe from the hilar plate and isolating the caudate lobe from the IVC and from the hepatic veins along with parenchymal resection.

Results
We report two successful cases with the Glissonean pedicle transection method described by Takasaki and the combined right- and left-side approach: a 63-year-old female patient with a 46-mm-in-diameter HCC tumor and a 39-year-old female patient with a 45-mm lesion and the pathological result was focal nodular hyperplasia.

Conclusions
We found this to be a safe and effective approach, which can be applied to all cases of benign tumors or in the case of malignant tumors located entirely in the caudate lobe when extended hepatic resection is not possible due to poor liver function or small remnant liver volume.
Association between gestational trophoblastic disease (GTD) history and clinical outcomes in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles
Authors: Cai Xinyu , Zhang Mei , Huang Chenyang , Jiang Yue , Zhou Jidong , Xu Manlin , Yan Guijun , Sun Haixiang , Kong Na 
Published: February 2022

Abstract
Background
Gestational trophoblastic disease (GTD) usually affects young women of childbearing age. After treatment for GTD, 86% of women wish to achieve pregnancy. On account of the impacts of GTD and treatments as well as patient anxiety, large numbers of couples turn to assisted reproductive technology (ART), especially in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). But few studies have investigated whether a history of GTD affects the outcomes of IVF/ICSI in secondary infertile patients and how it occurs. We investigate whether a history of GTD affects the IVF/ICSI outcomes and the live birth rates in women with secondary infertility.

Methods
This retrospective cohort study enrolled 176 women with secondary infertility who underwent IVF/ICSI treatment at the reproductive medical center of Nanjing Drum Tower Hospital from January 1, 2016, to December 31, 2020. Participants were divided into the GTD group (44 women with GTD history) and control group (132 women without GTD history matched from 8318 secondary infertile women). The control group and the study group were matched at a ratio of 3:1 according to patient age, infertility duration, number of cycles and body mass index (BMI). We assessed retrieved oocytes and high-grade embryos, biochemical pregnancy, miscarriage, ectopic pregnancy, gestational age at delivery, delivery mode and live birth rates.

Result(s)
We found a significantly reduced live-birth rate (34.1% vs 66.7%) associated with IVF/ICSI cycles in patients with a GTD history compared to those without a GTD history. The biochemical pregnancy and miscarriage rates of the GTD group were slightly higher than those of the control group. In addition, there was a difference in gestational age at delivery between the GTD and control groups (p < 0.001) but no differences in the mode of delivery (p = 0.267). Furthermore, the number of abandoned embryos in the GTD group was greater than that in the control group (p = 0.018), and the number of good-quality embryos was less than that in the control group (p = 0.019). The endometrial thickness was thinner (p < 0.001) in the GTD group. Immunohistochemistry (IHC) showed abnormal endometrial receptivity in the GTD group.

Conclusion(s)
The GTD history of patients undergoing IVF/ICSI cycles had an impact on the live-birth rate and gestational age at delivery, which might result from the thinner endometrium and abnormal endometrial receptivity before embryo transfer.
From GWAS to drug screening: repurposing antipsychotics for glioblastoma
Authors: Lin Wei-Zhi , Liu Yen-Chun , Lee Meng-Chang , Tang Chi-Tun , Wu Gwo-Jang , Chang Yu-Tien , Chu Chi-Ming , Shiau Chia-Yang 
Published: February 2022

Abstract
Background
Glioblastoma is currently an incurable cancer. Genome-wide association studies have demonstrated that 41 genetic variants are associated with glioblastoma and may provide an option for drug development.

Methods
We investigated FDA-approved antipsychotics for their potential treatment of glioblastoma based on genome-wide association studies data using a ‘pathway/gene-set analysis’ approach.

Results
The in-silico screening led to the discovery of 12 candidate drugs. DepMap portal revealed that 42 glioma cell lines show higher sensitivities to 12 candidate drugs than to Temozolomide, the current standard treatment for glioblastoma.

Conclusion
In particular, cell lines showed significantly higher sensitivities to Norcyclobenzaprine and Protriptyline which were predicted to bind targets to disrupt a certain molecular function such as DNA repair, response to hormones, or DNA-templated transcription, and may lead to an effect on survival-related pathways including cell cycle arrest, response to ER stress, glucose transport, and regulation of autophagy. However, it is recommended that their mechanism of action and efficacy are further determined.
A randomized clinical control study on the efficacy of three-dimensional upper limb robotic exoskeleton training in chronic stroke
Authors: Frisoli Antonio , Barsotti Michele , Sotgiu Edoardo , Lamola Giuseppe , Procopio Caterina , Chisari Carmelo 
Published: February 2022

AbstractBackgroundAlthough robotics assisted rehabilitation has proven to be effective in stroke rehabilitation, a limited functional improvements in Activities of Daily Life has been also observed after the administration of robotic training. To this aim in this study we compare the efficacy in terms of both clinical and functional outcomes of a robotic training performed with a multi-joint functional exoskeleton in goal-oriented exercises compared to a conventional physical therapy program, equally matched in terms of intensity and time. As a secondary goal of the study, it was assessed the capability of kinesiologic measurements—extracted by the exoskeleton robotic system—of predicting the rehabilitation outcomes using a set of robotic biomarkers collected at the baseline.MethodsA parallel-group randomized clinical trial was conducted within a group of 26 chronic post-stroke patients. Patients were randomly assigned to two groups receiving robotic or manual therapy. The primary outcome was the change in score on the upper extremity section of the Fugl-Meyer Assessment (FMA) scale. As secondary outcome a specifically designed bimanual functional scale, Bimanual Activity Test (BAT), was used for upper limb functional evaluation. Two robotic performance indices were extracted with the purpose of monitoring the recovery process and investigating the interrelationship between pre-treatment robotic biomarkers and post-treatment clinical improvement in the robotic group.ResultsA significant clinical and functional improvements in both groups (p < 0.01) was reported. More in detail a significantly higher improvement of the robotic group was observed in the proximal portion of the FMA (p < 0.05) and in the reduction of time needed for accomplishing the tasks of the BAT (p < 0.01). The multilinear-regression analysis pointed out a significant correlation between robotic biomarkers at the baseline and change in FMA score (R2 = 0.91, p < 0.05), suggesting their potential ability of predicting clinical outcomes.ConclusionExoskeleton-based robotic upper limb treatment might lead to better functional outcomes, if compared to manual physical therapy. The extracted robotic performance could represent predictive indices of the recovery of the upper limb. These results are promising for their potential exploitation in implementing personalized robotic therapy.Clinical Trial Registrationclinicaltrials.gov, NCT03319992 Unique Protocol ID: RH-UL-LEXOS-10. Registered 20.10.2017,https://clinicaltrials.gov/ct2/show/NCT03319992
COVID-19, sex, and gender in China: a scoping review
Authors: Feng Huiyun , Gan Connie Cai Ru , Leiva Diego , Zhang Bao Ling , Davies Sara E. 
Published: February 2022

Abstract
Background
During the course of the COVID-19 pandemic, states were called upon by the World Health Organization to introduce and prioritise the collection of sex-disaggregated data. The collection of sex-disaggregated data on COVID-19 testing, infection rates, hospital admissions, and deaths, when available, has informed our understanding of the biology of the infectious disease. The collection of sex-disaggregated data should also better inform our understanding of the gendered impacts that contribute to risk of exposure to COVID-19. In China, the country with the longest history of fighting the COVID-19 infection, what research was available on the gender-differential impacts of COVID-19 in the first 6 months of the COVID-19 pandemic?

Methods
In this scoping review, we examine the first 6 months (January–June 2020) of peer-reviewed publications (n = 451) on sex and gender experiences related to COVID-19 in China. We conducted an exhaustive search of published Chinese and English language research papers on COVID-19 in mainland China. We used a COVID-19 Gender Matrix informed by the JPHIEGO gender analysis toolkit to examine and illuminate research into the gendered impacts of COVID-19 within China.

Results
In China, only a small portion of the COVID-19-related research focused on gender experiences and differences. Near the end of the six-month literature review period, a small number of research items emerged on women healthcare workers, women’s mental health, and pregnant women’s access to care. There was an absence of research on the gendered impact of COVID-19 amongst populations. There was minimal consideration of the economic, social and security factors, including gender stereotypes and expectations, that affected different populations’ experiences of infection, treatment, and lockdown during the period of review.

Conclusion
At the outset of health emergencies in China, gender research needs to be prioritised during the first stage of an outbreak to assist with evaluation of the most effective public health measures, identifying access to healthcare and social welfare barriers amongst priority communities. Gender stereotypes and gendered differences lead to different patterns of exposure and treatment. The exclusion of this knowledge in real time affects the design of effective prevention and recovery.
Paramedic Norwegian Acute Stroke Prehospital Project (ParaNASPP) study protocol: a stepped wedge randomised trial of stroke screening using the National Institutes of Health Stroke Scale in the ambulance
Authors: Bugge Helge Fagerheim , Guterud Mona , Bache Kristi C. G. , Braarud Anne-Cathrine , Eriksen Erik , Fremstad Kjell Otto , Ihle-Hansen Hege , Ingebretsen Svein Håkon , Kramer-Johansen Jo , Larsen Karianne , Røislien Jo , Thorsen Kjetil , Toft Mathias , Sandset Else Charlotte , Hov Maren Ranhoff 
Published: February 2022

Abstract
Background
Less than 50% of stroke patients in Norway reach hospital within 4 h of symptom onset. Early prehospital identification of stroke and triage to the right level of care may result in more patients receiving acute treatment. Quality of communication between paramedics and the stroke centre directly affects prehospital on-scene time, emphasising this as a key factor to reduce prehospital delay. Prehospital stroke scales are developed for quick and easy identification of stroke, but have poor sensitivity and specificity compared to an in-hospital assessment with the National Institutes of Health Stroke Scale (NIHSS). The aim of the Paramedic Norwegian Acute Stroke Prehospital Project (ParaNASPP) is to assess whether a structured learning program, prehospital NIHSS and a mobile application facilitating communication with the stroke physician may improve triage of acute stroke patients.

Methods
A stepped wedge cluster randomised controlled intervention design will be used in this trial in Oslo, Norway. Paramedics at five ambulance stations will enrol adult patients with suspected stroke within 24 h of symptom onset. All paramedics will begin in a control phase with standard procedures. Through an e-learning program and practical training, a random and sequential switch to the intervention phase takes place. A mobile application for NIHSS scoring, including vital patient information for treatment decisions, transferring data from paramedics to the on-call stroke physician at the Stroke Unit at Oslo University Hospital, will be provided for the intervention.
The primary outcome measure is positive predictive value (PPV) for prehospital identification of patients with acute stroke defined as the proportion of patients accepted for stroke evaluation and discharged with a final stroke diagnosis. One thousand three hundred patients provide a 50% surplus to the 808 patients needed for 80% power to detect a 10% increase in PPV.

Discussion
Structured and digital communication using a common scale like NIHSS may result in increased probability for better identification of stroke patients and less stroke mimics delivered to a stroke team for acute diagnostics and treatment in our population.

Trial registration
ClinicalTrials.govNCT04137874. Registered on October 24, 2019.
High-dose vitamin D substitution in patients with COVID-19: study protocol for a randomized, double-blind, placebo-controlled, multi-center study—VitCov Trial
Authors: Jaun Fabienne , Boesing Maria , Lüthi-Corridori Giorgia , Abig Kristin , Makhdoomi Anja , Bloch Nando , Lins Christina , Raess Andrea , Grillmayr Victoria , Haas Philippe , Schuetz Philipp , Gabutti Luca , Muser Jürgen , Leuppi-Taegtmeyer Anne B. , Giezendanner Stéphanie , Brändle Michael , Leuppi Jörg D. 
Published: February 2022

Abstract
Background
The coronavirus disease 19 (COVID-19) pandemic has caused millions of deaths, and new treatments are urgently needed. Factors associated with a worse COVID-19 prognosis include old age (> 65 years), ethnicity, male sex, obesity, and people with comorbidities. Furthermore, vitamin D deficiency was reported as a predictor of poor prognosis in patients with acute respiratory failure due to COVID-19. According to a recent clinical case series, vitamin D deficiency is a modifiable risk factor, which has the prospect of reducing hospital stay, intensive care, and fatal outcomes. Vitamin D has potent immunomodulatory properties, and its supplementation might improve important outcomes in critically ill and vitamin D-deficient COVID-19 patients. Despite the evidence that supports an association between vitamin D deficiency and COVID-19 severity, there is uncertainty about the direct link. Therefore, the aim of the trial is to assess if high-dose vitamin D supplementation has a therapeutic effect in vitamin D-deficient patients with COVID-19.

Methods
As the trial design, a randomized, placebo-controlled, double-blind, multi-center approach was chosen to compare a high single dose of vitamin D (140,000 IU) followed by treatment as usual (TAU) (VitD + TAU) with treatment as usual only (placebo + TAU) in patients with COVID-19 and vitamin D deficiency.

Discussion
Vitamin D substitution in patients with COVID-19 and vitamin D deficiency should be investigated for efficacy and safety. The study aim is to test the hypothesis that patients with vitamin D deficiency suffering from COVID-19 treated under standardized conditions in hospital will recover faster when additionally treated with high-dose vitamin D supplementation. Latest studies suggest that vitamin D supplementation in patients with COVID-19 is highly recommended to positively influence the course of the disease. With this randomized controlled trial, a contribution to new treatment guidelines shall be made.

Trial registration
ClinicalTrials.gov NCT04525820 and SNCTP 2020-01401
Dental antibiotic stewardship: study protocol for developing international consensus on a core outcome set
Authors: Thompson Wendy , Teoh Leanne , Pulcini Céline , Williams David , Pitkeathley Carole , Carter Vanessa , Sanderson Susie , Torres Glauco , Walsh Tanya 
Published: February 2022

AbstractBackgroundAntimicrobial resistance is both a global public health and patient safety problem driven by overprescribing of antibiotic and other antimicrobial drugs. To conserve the effectiveness of antibiotics for future generations, antibiotic stewardship approaches to using them only where appropriate and necessary are advocated. Dentistry accounts for about 10% of antibiotic prescriptions across global healthcare, with 80% not in accordance with guidance in some countries. Core outcome sets enable the results of studies to be compared in order to maximise the value which can be derived from them. The aim of this study is to develop an international consensus on a core outcome set for dental antibiotic stewardship.MethodsConsensus on outcomes which are critical for inclusion in the core outcome set for dental antibiotic stewardship will be sought through two rounds of a Delphi survey (using the DelphiManager online system) followed by a final online consensus meeting. Thirty participants will be recruited to the Delphi Panel from across three stakeholder groups: ten dentists, ten academics and ten adults experienced with dental antibiotics as either a patient or parent/carer of a patient who has been prescribed them. Consensus will be achieved if more than 70% of the panel agree that an outcome is critical, with at least one from each stakeholder group in agreement. A long-list of candidate core outcomes has been developed from previously published studies with additions recommended by the steering group. The steering group will oversee development of the core outcome set and includes people from around the world with experience of dental antibiotics: clinicians, researchers and people with experience of being prescribed dental antibiotics and/or surviving an antibiotic resistant infection.DiscussionTo date, few studies of dental antibiotic stewardship have been published. Internationally, dental antibiotic guidelines and patterns of use vary widely, so a core outcome set is particularly important to facilitate meaningful comparisons between studies. This core outcome set will encompass antibiotic prescribing for both therapeutic indications, such as for people with acute infections, and for prophylactic indications, such as the prevention of distant site infections (like infective endocarditis) following dental procedures.
Accelerating neural network training with distributed asynchronous and selective optimization (DASO)
Authors: Coquelin Daniel , Debus Charlotte , Götz Markus , von der Lehr Fabrice , Kahn James , Siggel Martin , Streit Achim 
Published: February 2022

AbstractWith increasing data and model complexities, the time required to train neural networks has become prohibitively large. To address the exponential rise in training time, users are turning to data parallel neural networks (DPNN) and large-scale distributed resources on computer clusters. Current DPNN approaches implement the network parameter updates by synchronizing and averaging gradients across all processes with blocking communication operations after each forward-backward pass. This synchronization is the central algorithmic bottleneck. We introduce the distributed asynchronous and selective optimization (DASO) method, which leverages multi-GPU compute node architectures to accelerate network training while maintaining accuracy. DASO uses a hierarchical and asynchronous communication scheme comprised of node-local and global networks while adjusting the global synchronization rate during the learning process. We show that DASO yields a reduction in training time of up to 34% on classical and state-of-the-art networks, as compared to current optimized data parallel training methods.