bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isatuximab as monotherapy and combined with dexamethasone in patients with relapsed/refractory multiple myeloma
Authors: Dimopoulos Meletios , Bringhen Sara , Anttila Pekka , Capra Marcelo , Cavo Michele , Cole Craig , Gasparetto Cristina , Hungria Vania , Jenner Matthew , Vorobyev Vladimir , Ruiz Eduardo Yanez , Yin Jian Y. , Saleem Rao , Hellet Maeva , Macé Sandrine , Paiva Bruno , Vij Ravi 
Published: October 2020

Abstract
This phase 2 study evaluated isatuximab as monotherapy or combined with dexamethasone in relapsed/refractory multiple myeloma (RRMM). Patients had RRMM refractory to an immunomodulatory drug (IMiD) and a proteasome inhibitor (PI) or had received ≥3 prior lines of therapy incorporating an IMiD and PI. Patients received isatuximab either as monotherapy (20 mg/kg on days 1, 8, 15, and 22 [once weekly] of cycle 1 followed by 20 mg/kg on days 1 and 15 of subsequent cycles; Isa group) or in combination with dexamethasone (40 mg/d [20 mg/d in patients aged ≥75 years] once weekly; Isa-dex group). Treated patients (N = 164) had received a median of 4 (range, 2-10) prior treatment lines. Patients received a median of 5 (1-24) and 7 (1-22) treatment cycles; at data cutoff, 13 (11.9%) of 109 and 15 (27.3%) of 55 patients remained on treatment in the Isa and Isa-dex arms, respectively. Overall response rate (primary efficacy end point) was 23.9% in the Isa arm and 43.6% in the Isa-dex arm (odds ratio, 0.405; 95% confidence interval, 0.192-0.859; P = .008). Median progression-free survival and overall survival were 4.9 and 18.9 months for Isa, and 10.2 and 17.3 months for Isa-dex. Infusion reactions (mostly grade 1/2) and hematologic abnormalities were the most common adverse events. There was a similar incidence of grade 3 or higher infections in both groups (22.0% and 21.8%). In conclusion, addition of dexamethasone to isatuximab increased response rates and survival outcomes with no detrimental effect on safety. This trial was registered at www.clinicaltrials.gov as #NCT01084252.
Morphologic remission status is limited compared to ΔN flow cytometry: a Children’s Oncology Group AAML0531 report
Authors: Brodersen Lisa Eidenschink , Gerbing Robert B. , Pardo M. Laura , Alonzo Todd A. , Paine Dana , Fritschle Wayne , Hsu Fan-Chi , Pollard Jessica A. , Aplenc Richard , Kahwash Samir B. , Hirsch Betsy , Ramondi Susana , Wells Denise , Kolb E. Anders , Gamis Alan S. , Meshinchi Soheil , Loken Michael R. 
Published: October 2020

AbstractRisk stratification for acute myeloid leukemia (AML) uses molecular and cytogenetic abnormalities identified at diagnosis. Response to therapy informs risk, and morphology continues to be used more frequently than flow cytometry. Herein, the largest cohort of pediatric patients prospectively assessed for measurable residual disease (MRD) by flow cytometry (N = 784) is reported. The “difference from normal” (ΔN) technique was applied: 31% of all patients tested positive (AML range, 0.02% to 91%) after the first course of treatment on Children’s Oncology Group study AAML0531. Detection of MRD following initial chemotherapy proved the strongest predicator of overall survival (OS) in univariable and multivariable analyses, and was predictive of relapse risk, disease-free survival, and treatment-related mortality. Clearance of MRD after a second round of chemotherapy did not improve survival. The morphologic definition of persistent disease (&gt;15% AML) failed 27% of the time; those identified as MRD− had superior outcomes. Similarly, for patients not achieving morphologic remission (&gt;5% blasts), 36% of patients were MRD− and had favorable outcomes compared with those who were MRD+ (P &lt; .001); hence an increase in myeloid progenitor cells can be favorable when ΔN classifies them as phenotypically normal. Furthermore, ΔN reclassified 20% of patients in morphologic remission as having detectable MRD with comparable poor outcomes. Retrospective analysis using the relapse phenotype as a template demonstrated that 96% of MRD− patients had &lt;0.02% of the relapse immunophenotype in their end of induction 1 marrow. Thus, the detection of abnormal myeloid progenitor cells by ΔN is both specific and sensitive, with a high predictive signal identifiable early in treatment. This trial was registered at www.clinicaltrials.gov as #NCT00372593.
Allogeneic transplantation for Ph+ acute lymphoblastic leukemia with posttransplantation cyclophosphamide
Authors: Webster Jonathan A. , Luznik Leo , Tsai Hua-Ling , Imus Philip H. , DeZern Amy E. , Pratz Keith W. , Levis Mark J. , Gojo Ivana , Showel Margaret M. , Prince Gabrielle , Bolaños-Meade Javier , Gondek Lukasz P. , Ghiaur Gabriel , Dalton W. Brian , Jain Tania , Fuchs Ephraim J. , Gladstone Douglas E. , Gocke Christian B. , Ali Syed Abbas , Huff Carol Ann , Borrello Ivan M. , Swinnen Lode , Wagner-Johnston Nina , Ambinder Richard F. , Jones Richard J. , Smith B. Douglas 
Published: October 2020

Abstract
Allogeneic blood or marrow transplantation (alloBMT) is standard of care for adults with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) in first complete remission (CR1). The routine pretransplant and posttransplant use of tyrosine kinase inhibitors (TKIs) has dramatically improved outcomes, but the optimal conditioning regimen, donor type, and TKI remain undefined. The bone marrow transplant database at Johns Hopkins was queried for adult patients with de novo Ph+ ALL who received alloBMT using posttransplantation cyclophosphamide (PTCy) as a component of graft-versus-host disease (GVHD) prophylaxis from 2008 to 2018. Among transplants for Ph+ ALL, 69 (85%) were performed in CR1, and 12 (15%) were performed in second or greater remission (CR2+). The majority of transplants (58%) were HLA haploidentical. Nearly all patients (91.4%) initiated TKI posttransplant. For patients in CR1, the 5-year relapse-free survival (RFS) was 66%. The use of nonmyeloablative conditioning, absence of measurable residual disease (MRD) according to flow cytometry at transplant, and the use of dasatinib vs imatinib at diagnosis were associated with improved overall survival (OS) and RFS. Neither donor type nor recipient age ≥60 years affected RFS. When analyzing all transplants, alloBMT in CR1 (vs CR2+) and the absence of pretransplant MRD were associated with improved RFS. Most relapses were associated with the emergence of kinase domain mutations. The cumulative incidence of grade 3 to 4 acute GVHD at 1 year was 9%, and moderate to severe chronic GVHD at 2 years was 8%. Nonmyeloablative alloBMT with PTCy for Ph+ ALL in an MRD-negative CR1 after initial treatment with dasatinib yields favorable outcomes.
Design-based learning for a sustainable future: student outcomes resulting from a biomimicry curriculum in an evolution course
Authors: Fried Erin , Martin Andrew , Esler Alexa , Tran Antoine , Corwin Lisa 
Published: October 2020

AbstractBackgroundNational institutes and education initiatives emphasize the need to prepare future biologists to apply discoveries in science towards solving problems that are both social and scientific in nature. Research from socio-scientific, design-based, and problem-based learning demonstrates that contextualized, real-world tasks can improve students’ ability to apply their scientific knowledge in practical ways to navigate social problems. Biomimicry Design is an interdisciplinary field requiring biology and design skills; it informs the creation of sustainable designs through emulation of biological structures and functions that arise as a result of natural selection. Notably, engaging in biomimicry design targets an important biology and engineering learning outcome: understanding of how structure influences function. This study leveraged the practices of biomimicry along with those of design-based learning (DBL) to improve student outcomes in an evolutionary biology undergraduate course. Through DBL, the authors aimed to (1) ignite deeper understanding of how structure determines function in nature (a cross-disciplinary concept) and (2) help students to consider new ways this concept can benefit society (a science process skill).ResultsWe randomly assigned two sections of an upper-division evolutionary biology course to either a biomimicry DBL (DBL group) or species comparison (comparison group) curricular design. Students in the course were exposed to a 1-day lesson, then 1-weeklong case study, and then a final project focused on either biomimicry species-to-human design comparisons (DBL condition) or species-to-species comparisons (comparison condition). To assess the targeted outcomes, we analyzed students’ responses from a pre-post assessment. Students in the biomimicry section were more likely to apply their biological structure–function knowledge to societal benefits when leaving the course. Students in both sections showed comparable gains in structure–function understanding, but there was no change in the number of students who used misconception language in their post-course compared to pre-course responses.ConclusionsWe conclude that our DBL curriculum, above and beyond the comparison curriculum, may support students’ ability to apply biological concepts to societal benefits without compromising structure–function understanding. Overall, these results provide rationale for incorporating tasks situated in DBL to address socio-scientific issues in biology courses.
Transition towards sustainable pharmacy? The influence of public debates on policy responses to pharmaceutical contaminants in water
Authors: Schaub Simon , Braunbeck Thomas 
Published: October 2020

AbstractBackgroundDespite clear-cut scientific evidence for pharmaceutical contaminants causing adverse effects in aquatic life, the regulatory response in Germany has been weak. In principle, there are different policy approaches to address pharmaceutical contaminants: German water protection policies mostly follows a control approach, complemented by end-of-pipe solutions in some German states. The approach leaves the activities of key target groups, such as the pharmaceutical industry, largely unaffected. A stakeholder consultation initiated in 2016 by the German Federal Ministry of the Environment did not lead to significant changes in regulation. Empirical research in political science has shown that analysing the public debate can be helpful in explaining policy responses and, in particular, policy change. This study follows this approach and investigates whether the German policy response to pharmaceutical contaminants can be explained by characteristics of the public debate on the issue.ResultsA discourse network analysis based on newspaper reporting in Germany was conducted between 2013 and 2017 to investigate the public debate on pharmaceutical contaminants. German newspapers actually paid considerable attention to the issue. In fact, the debate was not controversial, and participating organisations expressed similar views with regard to the risk of the contaminants, the causes of contamination and the approaches to be taken to mitigate the release of contaminants to the environment. The main narrative in the debate was supportive to the current policy approach applied in Germany. There were no concerted efforts by organisations such as environmental organisations or ecological parties to mobilise for an alternative policy approach.ConclusionsThe low level of polarisation in the policy subsystem and the absence of a strong narrative mobilising a major policy change may explain the persistence of the policy approach to pharmaceutical contaminants applied in Germany. A significant change to the current approach in the near future seems unlikely. Nevertheless, literature in political science shows that a polarised public debate and a strong pro-change actor coalition often preceded policy change. Actors with an interest in stricter regulation might want to reconsider their mobilisation strategies.
Evaluation of the Autof MS1000 mass spectrometer in the identification of clinical isolates
Authors: Ma Qiong , Zhang Qi , Yuan Youhua , Yan Wenjuan , Wang Shanmei , Xu Junhong , Zhang Jiangfeng , Wang Yuming , Li Yi 
Published: October 2020

Abstract
Background
To evaluate the accuracy and performance of the Autof MS1000 mass spectrometer in bacteria and yeast identification, 2342 isolates were obtained from microbial cultures of clinical specimens (e.g. blood, cerebrospinal fluid, respiratory tract samples, lumbar puncture fluid, wound samples, stool, and urine) collected in 2019 in Henan Provincial People’s Hospital. Repetitive strains from the same patient were excluded. We tested the Autof MS1000 and Bruker Biotyper mass spectrometry systems and the classical biochemical identification system VITEK 2/API 20C AUX. Inconsistencies in strain identification among the three systems were identified by 16S rDNA and gene sequencing.

Results
At the species level, the Autof MS1000 and Bruker Biotyper systems had isolate identification accuracies of 98.9 and 98.5%, respectively. At the genus level, the Autof MS1000 and Bruker Biotyper systems were 99.7 and 99.4% accurate, respectively. The instruments did not significantly differ in identification accuracy at either taxonomic level. The frequencies of unreliable identification were 1.1% (26/2342) for the Autof MS1000 and 1.5% (34/2342) for the Bruker Biotyper. In vitro experiments demonstrated that the coincidence rate of the Autof MS1000 mass spectrometer in the identification of five types of bacteria was > 93%, the identification error rate was < 3%, and the no identification rate was 0. This indicates that the Autof MS1000 system is acceptable for identification.

Conclusions
The Autof MS1000 mass spectrometer can be utilised to identify clinical isolates. However, an upgradation of the database is recommended to correctly identify rare strains.
Towards unravelling Wolbachia global exchange: a contribution from the Bicyclus and Mylothris butterflies in the Afrotropics
Authors: Duplouy Anne , Pranter Robin , Warren-Gash Haydon , Tropek Robert , Wahlberg Niklas 
Published: October 2020

Abstract
Background
Phylogenetically closely related strains of maternally inherited endosymbiotic bacteria are often found in phylogenetically divergent, and geographically distant insect host species. The interspecies transfer of the symbiont Wolbachia has been thought to have occurred repeatedly, facilitating its observed global pandemic. Few ecological interactions have been proposed as potential routes for the horizontal transfer of Wolbachia within natural insect communities. These routes are however likely to act only at the local scale, but how they may support the global distribution of some Wolbachia strains remains unclear.

Results
Here, we characterize the Wolbachia diversity in butterflies from the tropical forest regions of central Africa to discuss transfer at both local and global scales. We show that numerous species from both the Mylothris (family Pieridae) and Bicyclus (family Nymphalidae) butterfly genera are infected with similar Wolbachia strains, despite only minor interclade contacts across the life cycles of the species within their partially overlapping ecological niches. The phylogenetic distance and differences in resource use between these genera rule out the role of ancestry, hybridization, and shared host-plants in the interspecies transfer of the symbiont. Furthermore, we could not identify any shared ecological factors to explain the presence of the strains in other arthropod species from other habitats, or even ecoregions.

Conclusion
Only the systematic surveys of the Wolbachia strains from entire species communities may offer the material currently lacking for understanding how Wolbachia may transfer between highly different and unrelated hosts, as well as across environmental scales.
Increased osteoprotegerin level is associated with impaired cardiovagal modulation in type-2 diabetic patients treated with oral antidiabetic drugs
Authors: Jasmine M. R. , Nanda Nivedita , Sahoo Jayaprakash , Velkumary S. , Pal G. K. 
Published: October 2020

Abstract
Background
An increased osteoprotegerin (OPG) level has been reported in both type-2 diabetes mellitus (T2DM) and cardiovascular diease (CVD) that are linked to sympathovagal imbalance (SVI). We explored the link of osteoprotegerin with cardiovagal modulation in T2DM.

Methods
We assessed fasting serum OPG, high-sensitive C-reactive protein (hsCRP), glucose, insulin and lipid profile in patients having T2DM receiving oral antidiabetic drugs (OAD) (n = 42) compared with age, gender and body composition-matched healthy participants without diabetes (n = 42). Rate pressure product (RPP), spectral indices of heart rate variability (HRV) and body composition were recorded in both the groups. Association of HOMA-IR and OPG with various parameters were assessed.

Results
Osteoprotegerin, HOMA-IR, hsCRP, coronary lipid risk factor were significantly increased, markers of cardiovagal modulation (TP, SDNN, RMSSD) were considerably decreased, ratio of low-frequency to high-frequency (LH-HF ratio), the indicator of SVI, and RPP, the marker of myocardial work stress were significantly higher in patients with diabetes, suggesting an overall elevated CVD risks in them. HOMA-IR was correlated with RMSSD, lipid risk factors and OPG. Rise in OPG was correlated with decreased cardiovagal modulation in patients with diabetes. There was significant contribution of OPG in decreasing TP, suggesting impaired cardiovagal modulation.

Conclusion
T2DM patients receiving OAD had higher cardiometabolic risks compared to age, gender and body composition-matched healthy individuals. Increased level of OPG is linked to decreased cardiovagal modulation in T2DM patients.
A hypocaloric high-protein diet supplemented with β-cryptoxanthin improves non-alcoholic fatty liver disease: a randomized controlled trial
Authors: Haidari Fatemeh , Hojhabrimanesh Abdollah , Helli Bizhan , Seyedian Seyed-Saeed , Ahmadi-Angali Kambiz , Abiri Behnaz 
Published: October 2020

Abstract
Background
Despite promising animal data, there is no randomized controlled trial (RCT) on the effects of high protein (HP)-diet and/or β-cryptoxanthin in non-alcoholic fatty liver disease (NAFLD). Aims: Safety and efficacy assessment of a hypocaloric HP-diet supplemented with β-cryptoxanthin in NAFLD.

Methods
Ninety-two Iranian NAFLD outpatients were recruited for this 12-week, single-center, parallel-group, double-blind RCT and randomized into 4 arms (n = 23): HP-diet and β-cryptoxanthin (hypocaloric HP-diet + β-cryptoxanthin), HP-diet (hypocaloric HP-diet + placebo), β-cryptoxanthin (standard hypocaloric diet + β-cryptoxanthin), and control (standard hypocaloric diet + placebo). Serum levels of liver enzymes and grade of hepatic steatosis were assessed at baseline and study endpoint as outcome measures.

Results
In the intention-to-treat population (N = 92), HP-diet and β-cryptoxanthin group experienced greater 12-week reductions in serum levels of liver enzymes than control group (mean difference for alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase: − 27.2, − 7.2, − 39.2, and − 16.3 IU/L, respectively; all p < 0.010). Clinical remission rate (achieving grade 0 hepatic steatosis) in HP-diet and β-cryptoxanthin group (82.6%) was also higher than other groups (13.0%, 17.4%, and 0.0% in HP-diet, β-cryptoxanthin, and control groups, respectively; p < 0.001). Sixteen patients reported minor adverse events.

Conclusion
A hypocaloric HP-diet supplemented with β-cryptoxanthin safely and efficaciously improves NAFLD.

Trial registration number

This trial was registered at https://www.irct.ir as IRCT2017060210181N10.
Subtotal (segment II–VIII) hepatectomy for bilateral diffuse hepatolithiasis with compensatory caudate lobe hypertrophy: a report of two cases
Authors: Wang Wei , Zhang ZiJie , Wang Jian 
Published: October 2020

Abstract
Background
Hepatolithiasis often leads to atrophy–hypertrophy complex due to bile duct obstruction, inflammation or infection in the affected liver segments and compensatory response in the normal segments. In severe bilateral diffuse cases, main liver can all be atrophic, leaving the caudate lobe to be extremely hypertrophic. Subtotal (segment II–VIII) hepatectomy can be an option in selected patients under such circumstances. Since rare cases have been reported, our study aims to highlight the preoperative evaluation and key points of this procedure.

Case presentation
Two patients with primary and secondary bilateral diffuse hepatolithiasis, respectively, were enrolled in this case series. The atrophy of the left and right liver with an exceeding hypertrophy of the caudate lobe were observed. Since the liver anatomy had completely been changed, contrast computed tomography, magnetic resonance imaging combined with 3D liver reconstruction were employed for comprehensive evaluation and pre-operational planning. The patients underwent standard subtotal (segment II–VIII) hepatectomy. During operation, the hepatoduodenal ligament around porta hepatis was dissected firstly to expose the hepatic artery, portal vein, bile duct and their branches successively. And then the vessels and bile duct to caudate lobe were preserved safely through cutting off the left and right hepatic artery, portal vein and bile duct at a safe point distal to the origin of the branches to caudate lobe. Operation time was 300 min and 360 min, respectively. Blood loss was 200 ml and 300 ml. No evidence of liver dysfunction, hepatolithiasis relapse or cholangitis was observed during the follow-up of 12 and 26 months.

Conclusions
Subtotal (segment II–VIII) hepatectomy may be one of several treatments possible in selected patients with compensatory caudate lobe hypertrophy caused by bilateral diffuse hepatolithiasis.
Detecting SARS-CoV-2 at point of care: preliminary data comparing loop-mediated isothermal amplification (LAMP) to polymerase chain reaction (PCR)
Authors: Österdahl Marc F. , Lee Karla A. , Lochlainn Mary Ni , Wilson Stuart , Douthwaite Sam , Horsfall Rachel , Sheedy Alyce , Goldenberg Simon D. , Stanley Christopher J. , Spector Tim D. , Steves Claire J. 
Published: October 2020

Abstract
Background
A cost effective and efficient diagnostic tool for COVID-19 as near to the point of care (PoC) as possible would be a game changer in the current pandemic. We tested reverse transcription loop mediated isothermal amplification (RT-LAMP), a method which can produce results in under 30 min, alongside standard methods in a real-life clinical setting.

Methods
This prospective service improvement project piloted an RT-LAMP method on nasal and pharyngeal swabs on 21 residents of a high dependency care home, with two index COVID-19 cases, and compared it to multiplex tandem reverse transcription polymerase chain reaction (RT-PCR). We recorded vital signs of patients to correlate clinical and laboratory information and calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of a single swab using RT-LAMP compared with the current standard, RT-PCR, as per Standards for Reporting Diagnostic Accuracy Studies (STARD) guidelines.

Results
The novel method accurately detected 8/10 RT-PCR positive cases and identified a further 3 positive cases. Eight further cases were negative using both methods. Using repeated RT-PCR as a “gold standard”, the sensitivity and specificity of a single novel test were 80 and 73% respectively. PPV was 73% and NPV was 83%. Incorporating retesting of low signal RT-LAMP positives improved the specificity to 100%. We also speculate that hypothermia may be a significant early clinical sign of COVID-19.

Conclusions
RT-LAMP testing for SARS-CoV-2 was found to be promising, fast and to work equivalently to RT-PCR methods. RT-LAMP has the potential to transform COVID-19 detection, bringing rapid and accurate testing to the PoC. RT-LAMP could be deployed in mobile community testing units, care homes and hospitals to detect disease early and prevent spread.