bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anticancer bispecific antibody R&D advances: a study focusing on research trend worldwide and in China
Authors: Zhang Zhonghan , Luo Fan , Cao Jiaxin , Lu Feiteng , Zhang Yang , Ma Yuxiang , Zeng Kangmei , Zhang Li , Zhao Hongyun 
Published: August 2021

Abstract
Background
The bispecific antibody (bsAbs) research around the world has undergone great changes. We analyzed the global trend of bsAbs research and compared the differences in clinical research of bsAbs between China and worldwide.

Methods
BsAbs research clinical trials information was retrieved through the online open-resource clinical trial registration platform. Research information including organizations, identity numbers, locations, phases, participating centers, conditions, status, enrollment, targets, spectrums of mechanism of action (MOA), and start date was collected. Clinical trials were divided into two categories based on the attributes of pharmaceutical companies (international or China-initiated or involved).

Results
From 1997 to 2020, 272 clinical trials regarding bsAbs research were retrieved. Twenty-nine percent of the studies were contributed by companies from Chinese institutions, which followed the USA and ranked second. The clinical trials of bsAbs are mainly concentrated on phase I (n = 161), phase I/II (n = 54), and phase II (n = 51), and the number of phase III trials is still rare (n = 4). Tumor species distribution analysis shows that there are significantly higher focuses on gastric cancer (n = 18), esophageal/gastroesophageal junction cancer (n = 16), bladder cancer (n = 10), biliary malignant tumor (n = 8), nasopharyngeal cancer (n = 6), and thymic cancer (n = 2) in China. BsAbs target and spectrums of MOA analysis showed that international companies mainly focus on bsAbs with CD3-based (n = 63) target with MOA of T-cell redirection, while researches in China pay more attention to PD-1 (n = 9)/PD-L1 (n = 7) axises with MOA of double immune checkpoint blocking.

Conclusion
Global bsAbs research increased rapidly during the 1997 to 2020 period. The developed countries in America and Europe are leading the trend of bsAbs research. Anticancer bsAbs clinical research in China is booming and chasing after the world trend.
The varying effects of antibiotics on gut microbiota
Authors: Yang Lulu , Bajinka Ousman , Jarju Pa Omar , Tan Yurong , Taal Aji Mary , Ozdemir Guven 
Published: August 2021

AbstractAntibiotics are lifesaving therapeutic drugs that have been used by human for decades. They are used both in the fight against bacterial pathogens for both human and for animal feeding. However, of recent, their effects on the gut microbial compositions and diversities have attracted much attention. Existing literature have established the dysbiosis (reduced diversity) in the gut microbiota in association with antibiotic and antibiotic drug doses. In the light of spelling out the varying effects of antibiotic use on gut microbiota, this review aimed at given an account on the degree of gut microbial alteration caused by common antibiotics. While some common antibiotics are found to destroy the common phyla, other debilitating effects were observed. The effects can be attributed to the mode of mechanism, the class of antibiotic, the degree of resistance of the antibiotic used, the dosage used during the treatment, the route of administration, the pharmacokinetic and pharmacodynamics properties and the spectrum of the antibiotic agent. Health status, stress or the type of diet an individual feeds on could be a great proportion as confounding factors. While it is understood that only the bacterial communities are explored in the quest to establishing the role of gut in health, other gut microbial species are somehow contributing to the dysbiosis status of the gut microbiota. Until now, long term natural fluctuations like diseases outbreaks and mutations of the strain might as well rendered alteration to the gut independent of antibiotic treatments.
Production of R- and S-1,2-propanediol in engineered Lactococcus lactis
Authors: Sato Rintaro , Ikeda Motoyuki , Tanaka Tomonari , Ohara Hitomi , Aso Yuji 
Published: August 2021

Abstract1,2-propanediol (1,2-PDO) is a versatile chemical used in multiple manufacturing processes. To date, some engineered and non-engineered microbes, such as Escherichia coli, Lactobacillus buchneri, and Clostridium thermosaccharolyticum, have been used to produce 1,2-PDO. In this study, we demonstrated the production of R- and S-1,2-PDO using engineered Lactococcus lactis. The L- and D-lactic acid-producing L. lactis strains NZ9000 and AH1 were transformed with the plasmid pNZ8048-ppy harboring pct, pduP, and yahK genes for 1,2-PDO biosynthesis, resulting in L. lactis LL1 and LL2, respectively. These engineered L. lactis produced S- and R-1,2-PDO at concentrations of 0.69 and 0.50 g/L with 94.4 and 78.0% ee optical purities, respectively, from 1% glucose after 72 h of cultivation. Both 1% mannitol and 1% gluconate were added instead of glucose to the culture of L. lactis LL1 to supply NADH and NADPH to the 1,2-PDO production pathway, resulting in 75% enhancement of S-1,2-PDO production. Production of S-1,2-PDO from 5% mannitol and 5% gluconate was demonstrated using L. lactis LL1 with a pH–stat approach. This resulted in S-1,2-PDO production at a concentration of 1.88 g/L after 96 h of cultivation. To our knowledge, this is the first report on the production of R- and S-1,2-PDO using engineered lactic acid bacteria.
Comparison of four channelled videolaryngoscopes to Macintosh laryngoscope for simulated intubation of critically ill patients: the randomized MACMAN2 trial
Authors: Decamps Paul , Grillot Nicolas , Le Thuaut Aurelie , Brule Noelle , Lejus-Bourdeau Corinne , Reignier Jean , Lascarrou Jean-Baptiste 
Published: August 2021

Abstract
Background
Videolaryngoscopes with an operating channel may improve the intubation success rate in critically ill patients. We aimed to compare four channelled videolaryngoscopes to the Macintosh laryngoscope used for intubation of a high-fidelity simulation mannikin, in a scenario that simulated critical illness due to acute respiratory failure.

Results
Of the 79 residents who participated, 54 were considered inexperienced with orotracheal intubation. Each participant used all five devices in random order. The first-pass success rate was 97.5% [95% CI 91.1–99.7] for Airtraq™, KingVision™, and Pentax AWS200™, 92.4% [95% CI 84.2–97.2] for VividTrac VT-A100™, and 70.9% [95% CI 59.6–80.6] for direct Macintosh laryngoscopy. The first-pass success rate was significantly lower with direct Macintosh laryngoscopy than with the videolaryngoscopes (p  <  0.0001 for Airtraq™, KingVision™, Pentax AWS200™, and VividTrac VT-A100™).

Conclusion
The Airtraq™, KingVision™, and Pentax AWS200™ channelled videolaryngoscopes produced high first-pass success rates with a lower boundary of the 95% CI above 90%. A multicentre, randomised controlled clinical study comparing channelled videolaryngoscopy to direct laryngoscopy should include one of these three videolaryngoscopes.
Metabolic convergence on lipogenesis in RAS, BCR-ABL, and MYC-driven lymphoid malignancies
Authors: Liefwalker Daniel F. , Ryan Meital , Wang Zhichao , Pathak Khyatiben V. , Plaisier Seema , Shah Vidhi , Babra Bobby , Dewson Gabrielle S. , Lai Ian K. , Mosley Adriane R. , Fueger Patrick T. , Casey Stephanie C. , Jiang Lei , Pirrotte Patrick , Swaminathan Srividya , Sears Rosalie C. 
Published: August 2021

AbstractBackgroundMetabolic reprogramming is a central feature in many cancer subtypes and a hallmark of cancer. Many therapeutic strategies attempt to exploit this feature, often having unintended side effects on normal metabolic programs and limited efficacy due to integrative nature of metabolic substrate sourcing. Although the initiating oncogenic lesion may vary, tumor cells in lymphoid malignancies often share similar environments and potentially similar metabolic profiles. We examined cells from mouse models of MYC-, RAS-, and BCR-ABL-driven lymphoid malignancies and find a convergence onde novolipogenesis. We explore the potential role of MYC in mediating lipogenesis by13C glucose tracing and untargeted metabolic profiling. Inhibition of lipogenesis leads to cell death bothin vitroandin vivoand does not induce cell death of normal splenocytes.MethodsWe analyzed RNA-seq data sets for common metabolic convergence in lymphoma and leukemia. Usingin vitrocell lines derived in from conditional MYC, RAS, and BCR-ABL transgenic murine models and oncogene-driven human cell lines, we determined gene regulation, metabolic profiles, and sensitivity to inhibition of lipogenesis in lymphoid malignancies. We utilize preclinical murine models and transgenic primary model of T-ALL to determine the effect of lipogenesis blockade across BCR-ABL-, RAS-, and c-MYC-driven lymphoid malignancies. Statistical significance was calculated using unpairedt-tests and one-way ANOVA.ResultsThis study illustrates thatde novolipid biogenesis is a shared feature of several lymphoma subtypes. Using cell lines derived from conditional MYC, RAS, and BCR-ABL transgenic murine models, we demonstrate shared responses to inhibition of lipogenesis by the acetyl-coA carboxylase inhibitor 5-(tetradecloxy)-2-furic acid (TOFA), and other lipogenesis inhibitors. We performed metabolic tracing studies to confirm the influence of c-MYC and TOFA on lipogenesis. We identify specific cell death responses to TOFAin vitroandin vivoand demonstrate delayed engraftment and progressionin vivoin transplanted lymphoma cell lines. We also observe delayed progression of T-ALL in a primary transgenic mouse model upon TOFA administration. In a panel of human cell lines, we demonstrate sensitivity to TOFA treatment as a metabolic liability due to the general convergence onde novolipogenesis in lymphoid malignancies driven by MYC, RAS, or BCR-ABL. Importantly, cell death was not significantly observed in non-malignant cellsin vivo.ConclusionsThese studies suggest thatde novolipogenesis may be a common survival strategy for many lymphoid malignancies and may be a clinically exploitable metabolic liability.Trial registrationThis study does not include any clinical interventions on human subjects.
Patient–ventilator asynchrony, impact on clinical outcomes and effectiveness of interventions: a systematic review and meta-analysis
Authors: Kyo Michihito , Shimatani Tatsutoshi , Hosokawa Koji , Taito Shunsuke , Kataoka Yuki , Ohshimo Shinichiro , Shime Nobuaki 
Published: August 2021

Abstract
Background
Patient–ventilator asynchrony (PVA) is a common problem in patients undergoing invasive mechanical ventilation (MV) in the intensive care unit (ICU), and may accelerate lung injury and diaphragm mis-contraction. The impact of PVA on clinical outcomes has not been systematically evaluated. Effective interventions (except for closed-loop ventilation) for reducing PVA are not well established.

Methods
We performed a systematic review and meta-analysis to investigate the impact of PVA on clinical outcomes in patients undergoing MV (Part A) and the effectiveness of interventions for patients undergoing MV except for closed-loop ventilation (Part B). We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, ClinicalTrials.gov, and WHO-ICTRP until August 2020. In Part A, we defined asynchrony index (AI) ≥ 10 or ineffective triggering index (ITI) ≥ 10 as high PVA. We compared patients having high PVA with those having low PVA.

Results
Eight studies in Part A and eight trials in Part B fulfilled the eligibility criteria. In Part A, five studies were related to the AI and three studies were related to the ITI. High PVA may be associated with longer duration of mechanical ventilation (mean difference, 5.16 days; 95% confidence interval [CI], 2.38 to 7.94; n = 8; certainty of evidence [CoE], low), higher ICU mortality (odds ratio [OR], 2.73; 95% CI 1.76 to 4.24; n = 6; CoE, low), and higher hospital mortality (OR, 1.94; 95% CI 1.14 to 3.30; n = 5; CoE, low). In Part B, interventions involving MV mode, tidal volume, and pressure-support level were associated with reduced PVA. Sedation protocol, sedation depth, and sedation with dexmedetomidine rather than propofol were also associated with reduced PVA.

Conclusions
PVA may be associated with longer MV duration, higher ICU mortality, and higher hospital mortality. Physicians may consider monitoring PVA and adjusting ventilator settings and sedatives to reduce PVA. Further studies with adjustment for confounding factors are warranted to determine the impact of PVA on clinical outcomes.
Trial registration protocols.io (URL: https://www.protocols.io/view/the-impact-of-patient-ventilator-asynchrony-in-adu-bsqtndwn, 08/27/2020).
Prediction of geomagnetically induced currents (GICs) flowing in Japanese power grid for Carrington-class magnetic storms
Authors: Ebihara Yusuke , Watari Shinichi , Kumar Sandeep 
Published: August 2021

AbstractLarge-amplitude geomagnetically induced currents (GICs) are the natural consequences of the solar–terrestrial connection triggered by solar eruptions. The threat of severe damage of power grids due to the GICs is a major concern, in particular, at high latitudes, but is not well understood as for low-latitude power grids. The purpose of this study is to evaluate the lower limit of the GICs that could flow in the Japanese power grid against a Carrington-class severe magnetic storm. On the basis of the geomagnetic disturbances (GMDs) observed at Colaba, India, during the Carrington event in 1859, we calculated the geoelectric disturbances (GEDs) by a convolution theory, and calculated GICs flowing through transformers at 3 substations in the Japanese extra-high-voltage (500-kV) power grid by a linear combination of the GEDs. The estimated GEDs could reach ~ 2.5 V/km at Kakioka, and the GICs could reach, at least, 89 ± 30 A near the storm maximum. These values are several times larger than those estimated for the 13–14 March 1989 storm (in which power blackout occurred in Canada), and the 29–31 October 2003 storm (in which power blackout occurred in Sweden). The GICs estimated here are the lower limits, and there is a probability of stronger GICs at other substations. The method introduced here will be immediately applicable for benchmark evaluation of low-latitude GICs against the Carrington-class magnetic storms if one assumes electrical parameters, such as resistance of transmission lines, with sufficient accuracy.
Cell-free osteochondral scaffolds provide a substantial clinical benefit in the treatment of osteochondral defects at a minimum follow-up of 5 years
Authors: Ricci Martina , Tradati Daniele , Maione Alessio , Uboldi Francesco Mattia , Usellini Eva , Berruto Massimo 
Published: August 2021

Abstract
Purpose
The treatment of osteochondral lesions is challenging and no consensus has been established about the best option for restoring both cartilage and subchondral bone. Multilayer collagen-hydroxyapatite scaffolds have shown promising clinical results, but the outcome at a follow-up longer than 5 years still has to be proved. The aim was to evaluate the clinical outcome of patients with a knee isolated osteochondral lesion treated with a biomimetic three-layered scaffold at a minimum 5 years of follow-up.

Methods
Twenty-nine patients (23 males and 6 females, mean age 31.5 ± 11.4 years) were evaluated retrospectively before surgery, at 1 and 2 years and at last follow-up (FU). Visual Analog Scale (VAS) for pain, International Knee Documentation Committee (IKDC) Subjective Score, Tegner-Lysholm Knee Scoring Scale and Tegner Activity Level Scale were collected. Mean FU was 7.8 ± 2.0 years (min 5.1 - max 11.3). The etiology of the defect was Osteochondritis Dissecans or osteonecrosis (17 vs 12 cases).

Results
At 12 months FU the IKDC score improved from 51.1 ± 21.7 to 80.1 ± 17.9 (p < 0.01), Tegner Lysholm Score from 59.9 ± 17.3 to 92.5 ± 9.0 (p < 0.01), VAS from 6.1 ± 2.1 to 1.7 ± 2.3 (p < 0.01) and Tegner Activity Level Scale from 1.6 ± 0.5 to 4.9 ± 1.7 (p < 0.01). The results remained stable at 24 months, while at last FU a statistically significant decrease in IKDC, Tegner Lysholm and Tegner Activity Scale was recorded, though not clinically relevant. Patients under 35 achieved statistically better outcomes.

Conclusions
The use of a cell-free collagen-hydroxyapatite osteochondral scaffold provides substantial clinical benefits in the treatment of knee osteochondral lesions at a minimum follow-up of 5 years, especially in patients younger than 35 years.

Level of evidence
Level IV.
In vivo optical quality of posterior-chamber phakic implantable collamer lenses with a central port
Authors: Montés-Micó Robert , Pastor-Pascual Francisco , Artiaga-Elordi Enrique , Ruiz-Mesa Ramón , Tañá-Rivero Pedro 
Published: August 2021

Abstract
Background
The aim of this review is to summarize the optical quality results in patients following the implantation of the V4c implantable collamer lens with a central port (ICL, STAAR Surgical Inc.).

Main text
A literature search in several databases was carried out to identify those publications, both prospective, retrospective and/or comparative with other refractive surgery procedures, reporting optical outcomes of patients who were implanted with the V4c ICL model. A total of 17 clinical studies published between 2012 and 2021 were included in this review. A detailed analysis of the available data was performed including number of eyes, follow-up and preoperative spherical equivalent. Specifically, the review focused on several optical parameters including higher-order aberrations (HOAs), modulation transfer function (MTF) cut-off frequency and Strehl ratio. This review encompassed a total of 817 eyes measured using different optical devices based on Hartmann-Shack, retinal image quality measurement and ray-tracing technologies at different follow-ups.

Conclusions
The outcomes found in this review lead us to conclude that the ICL V4c model provides good optical quality, by means of different metrics, when implanted.
Effects of harvest intensity on the marketable organ yield, growth and reproduction of non-timber forest products (NTFPs): implication for conservation and sustainable utilization of NTFPs
Authors: Zhang Ting , Yu Lizhong , Man Yuan , Yan Qiaoling 
Published: August 2021

Abstract
Background
Non-timber forest products (NTFPs) are an important part of forest biodiversity, and the subsistence and trade of local people, especially in less developed countries. Because of the high ecological and economic value, NTFPs have faced the problem of over-exploitation, and the key to solve this problem is to determine the feasible way of sustainable utilization of NTFPs. Harvest intensity is one of the most important and easily controlled utilization factors, which can greatly influence the plant individual survival, growth and reproductive performances, and even the population structure and dynamics. Therefore, we chose two common and important NTFPs species with different marketable parts (i.e., Acanthopanax senticosus with tender leaves and Aralia elata with tender buds) as our study objects. Aiming to determine the optimum harvest intensity for sustainably utilizing both NTFPs species, five levels of harvest intensity treatments (i.e., control, light, medium, high and severe) were designed to assess the effects of harvest intensity on their marketable organ yield, plant growth and reproductive performances.

Results
The biomass growth rates of marketable organ and plant growth of A. senticosus under light harvest intensity treatment were significantly higher than those under other harvest intensities. The plant height growth and 1000-seed weight of A. elata under severe harvest intensity treatment were significantly lower than those under control treatment.

Conclusions
The light harvest intensity with 25% leaf removal and the high harvest intensity with all terminal buds harvested are the optimum harvest intensity to maintain the sustainable utilization of A. senticosus and A. elata, respectively. These findings could provide managers with basic but practical guidance for making decisions about the sustainable harvest management plan for the cultivated NTFPs species, and further provide a theoretical basis for managers to establish the harvest regulations for wild NTFPs species. Consequently, the local residents or communities can improve their income while ensure the sustainable development of wild NTFPs.
Systolic anterior motion of the mitral valve associated with acute type A aortic dissection: a case report describing one-step surgery of ascending aortic replacement and interventricular septal myectomy
Authors: Yamamoto Naoki , Onoda Koji 
Published: August 2021

Abstract
Background
Systolic anterior motion of the mitral valve associated with acute type A aortic dissection is rare in daily clinical practice. The prevention of systolic anterior motion is important, because once it occurs, the hemodynamics may become unstable, leading to a critical situation. In the surgical procedure to treat systolic anterior motion, the prevention of new iatrogenic aortic intimal tears is important in the context of acute type A aortic dissection.

Case presentation
We present a case of systolic anterior motion in a 68-year-old woman with an acute type A aortic dissection and suspected acute relative adrenal insufficiency. Preoperative transthoracic echocardiography revealed left ventricular outflow tract obstruction due to systolic anterior motion without left ventricular hypertrophy and interventricular septal bulging due to a narrow aorto-mitral angle. We successfully performed a one-step surgery for ascending aortic replacement and interventricular septal myectomy using the needle stick technique for the treatment of systolic anterior motion.

Conclusions
Concomitant interventricular septal myectomy using the needle stick technique with thoracic aortic replacement is a safe and feasible technique. Interventricular septal myectomy may be effective in preventing postoperative unstable hemodynamics due to systolic anterior motion in the management of acute aortic dissection.
What explains the technical efficiency of banks in Tunisia? Evidence from a two-stage data envelopment analysis
Authors: Jelassi Mohamed Mehdi , Delhoumi Ezzeddine 
Published: August 2021

AbstractIn this study we examine the potential determinants of technical efficiency for the Tunisian commercial banking sector over the period of 1995–2017. First, we estimate banking technical efficiency with a radial and non-radial bootstrap data envelopment analysis. For the radial technique, we use an input-oriented approach and for non-radial we use the Range Adjusted Measure (RAM). Second, we use a double bootstrapping regression technique to estimate the influence of a set of eventual determinants on technical efficiency. Finally, based on all possible regressions, we gauge the overall effect of each determinant. Our results reveal that the input-oriented and RAM approach gave somewhat similar results. We found that the return on equity, the expense to income ratio, the loan to deposit ratio, and the growth rate are insignificant to Tunisian banking technical efficiency. In particular, banking technical efficiency increases with capitalization and inflation, whereas, it decreases with size, number of bank branches, management to staff ratio, and loan to asset ratio. In addition, we identified evidence supporting the moderate success of the last decade of reforms and a noticeable one for the post-revolution reforms in helping improve banking technical efficiency. The post-revolution reforms, largely revolving around reinforcing the rules of good governance and banking supervision, coupled with the restructuring of public banks, were found to be insufficient to raise overall banking technical efficiency despite improvement in the technical efficiency of private banks.