bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pembrolizumab plus dinaciclib in patients with hematologic malignancies: the phase 1b KEYNOTE-155 study
Authors: Gregory Gareth P. , Kumar Shaji , Wang Ding , Mahadevan Daruka , Walker Patricia , Wagner-Johnston Nina , Escobar Carolina , Bannerji Rajat , Bhutani Divaya , Chang Julie , Hernandez-Ilizaliturri Francisco J. , Klein Andreas , Pagel John M. , Rybka Witold , Yee Andrew J. , Mohrbacher Anne , Huang Mo , Farooqui Mohammed , Marinello Patricia , Quach Hang 
Published: December 2021

AbstractPreclinical data demonstrated that combining an anti–programmed cell death 1 (PD-1) inhibitor with a cyclin-dependent kinase 9 (CDK9) inhibitor provided enhanced antitumor activity with no significant toxicities, suggesting this combination may be a potential therapeutic option. The multicohort, phase 1 KEYNOTE-155 study evaluated the safety and antitumor activity of the PD-1 inhibitor pembrolizumab plus the CDK9 inhibitor dinaciclib in patients with relapsed or refractory (rr) chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL) and multiple myeloma (MM). Patients enrolled were ≥18 years of age with a confirmed diagnosis of CLL, DLBCL, or MM. The study included 2 phases: a dose-evaluation phase to determine dose-limiting toxicities and a signal-detection phase. Patients received pembrolizumab 200 mg every 3 weeks plus dinaciclib 7 mg/m2 on day 1 and 10 mg/m2 on day 8 of cycle 1 and 14 mg/m2 on days 1 and 8 of cycles 2 and later. Primary endpoint was safety, and a key secondary endpoint was objective response rate (ORR). Seventy-two patients were enrolled and received ≥1 dose of study treatment (CLL, n = 17; DLBCL, n = 38; MM, n = 17). Pembrolizumab plus dinaciclib was generally well tolerated and produced no unexpected toxicities. The ORRs were 29.4% (5/17, rrCLL), 21.1% (8/38, rrDLBCL), and 0% (0/17, rrMM), respectively. At data cutoff, all 72 patients had discontinued treatment, 38 (52.8%) because of progressive disease. These findings demonstrate activity with combination pembrolizumab plus dinaciclib and suggest that a careful and comprehensive approach to explore anti–PD-1 and CDK9 inhibitor combinations is warranted. This trial was registered at www.clinicaltrials.gov as NCT02684617.
Deterioration of headache impact and health-related quality of life in migraine patients after cessation of preventive treatment with CGRP(−receptor) antibodies
Authors: Terhart Maria , Mecklenburg Jasper , Neeb Lars , Overeem Lucas Hendrik , Siebert Anke , Steinicke Maureen , Raffaelli Bianca , Reuter Uwe 
Published: December 2021

AbstractBackgroundMigraine preventive treatment with CGRP(−receptor) monoclonal antibodies (mAbs) has a positive effect on patients’ health-related quality of life (HRQoL). The German treatment guidelines recommend discontinuing successful treatment with CGRP(−receptor) mAbs after 6–12 months. We aimed to evaluate headache-specific and generic HRQoL for three months after discontinuation of CGRP(−receptor) mAb treatment.MethodsWe conducted a prospective, longitudinal cohort study, including patients with migraine after 8–12 months of therapy with a CGRP(−R) mAb and before a planned discontinuation attempt. HRQoL was assessed at the time of the last mAbs injection (V1), eight weeks later (V2), and sixteen weeks later (V3). For headache-specific HRQoL, we used the Headache Impact Test-6 (HIT-6). Generic HRQoL was determined with the EuroQol-5-Dimension-5-Level (ED-5D-5L) form, and the Short-Form 12 (SF-12), which comprises a Physical Component Summary (PCS-12) and a Mental Component Summary (MCS-12).Questionnaires’ total scores were compared across the three observation points using nonparametric procedures.ResultsThe study cohort consisted ofn = 61 patients (n = 29 treated with the CGRP-receptor mAb erenumab andn = 32 with the CGRP mAbs galcanezumab or fremanezumab). The HIT-6 sum score was 59.69 ± 6.90 at V1 and increased by 3.69 ± 6.21 at V3 (p < 0.001), indicating a greater headache impact on patients’ lives. The mean total EQ-D5-L5 score declined from 0.85 ± 0.17 at V1 by − 0.07 ± 0.18 at V3 (p = 0.013). Both Mental and Physical Component Scores of the SF-12 worsened significantly during treatment discontinuation: The PCS-12 total score decreased by − 4.04 ± 7.90 from V1 to V3 (p = 0.013) and the MCS-12 score by − 2.73 ± 9.04 (p = 0.003). Changes in all questionnaires’ scores but the MCS-12 were already significant in the first month of the drug holiday (V2).ConclusionsOur results show a significant decline in headache impact and generic HRQoL of migraine patients after treatment discontinuation of a CGRP(−R) mAb. The observed deterioration is above the established minimally clinically important differences for each of the questionnaires and can therefore be considered clinically meaningful. Monitoring HRQoL during a discontinuation attempt could facilitate the decision whether or not to resume preventive treatment with CGRP(−R) mAbs.
Quantitative assessment of the central versus peripheral effect of intravenous clonidine using baroreflex equilibrium diagrams
Authors: Kawada Toru , Nishikawa Takuya , Hayama Yohsuke , Li Meihua , Zheng Can , Uemura Kazunori , Saku Keita , Miyamoto Tadayoshi , Sugimachi Masaru 
Published: December 2021

AbstractClonidine is a first-generation central antihypertensive that reduces sympathetic nerve activity (SNA). Although clonidine also exerts peripheral vasoconstriction, the extent to which this vasoconstriction offsets the centrally mediated arterial pressure (AP)-lowering effect remains unknown. In anesthetized rats (n = 8), we examined SNA and AP responses to stepwise changes in carotid sinus pressure under control conditions and after intravenous low-dose (2 μg/kg) and high-dose clonidine (5 μg/kg). In the baroreflex equilibrium diagram analysis, the operating-point AP under the control condition was 115.2 (108.5–127.7) mmHg [median (25th–75th percentile range)]. While the operating-point AP after low-dose clonidine was not significantly different with or without the peripheral effect, the operating-point AP after high-dose clonidine was higher with the peripheral effect than without [81.3 (76.2–98.2) mmHg vs. 70.7 (57.7–96.9), P < 0.05]. The vasoconstrictive effect of clonidine partly offset the centrally mediated AP-lowering effect after high-dose administration.
Myocardial injury in hospitalized COVID-19 patients: a retrospective study, systematic review, and meta-analysis
Authors: Changal Khalid , Veria Spiro , Mack Sean , Paternite David , Sheikh Shoaib Altaf , Patel Mitra , Mir Tanveer , Sheikh Mujeeb , Ramanathan P. Kasi 
Published: December 2021

Abstract
Introduction
The majority of studies evaluating the effect of myocardial injury on the survival of COVID-19 patients have been performed outside of the United States (U.S.). These studies have often utilized definitions of myocardial injury that are not guideline-based and thus, not applicable to the U.S. patient population.

Methods
The current study is a two-part investigation of the effect of myocardial injury on the clinical outcome of patients hospitalized with COVID-19. The first part is a retrospective analysis of 268 patients admitted to our healthcare system in Toledo, Ohio, U.S.; the second part is a systematic review and meta-analysis of all similar studies performed within the U.S.

Results
In our retrospective analysis, patients with myocardial injury were older (mean age 73 vs. 59 years, P 0.001), more likely to have hypertension (86% vs. 67%, P 0.005), underlying cardiovascular disease (57% vs. 24%, P 0.001), and chronic kidney disease (26% vs. 10%, P 0.004). Myocardial injury was also associated with a lower likelihood of discharge to home (35% vs. 69%, P 0.001), and a higher likelihood of death (33% vs. 10%, P 0.001), acute kidney injury (74% vs. 30%, P 0.001), and circulatory shock (33% vs. 12%, P 0.001). Our meta-analysis included 12,577 patients from 8 U.S. states and 55 hospitals who were hospitalized with COVID-19, with the finding that myocardial injury was significantly associated with increased mortality (HR 2.43, CI 2.28–3.6, P 0.0005). The prevalence of myocardial injury ranged from 9.2 to 51%, with a mean prevalence of 27.2%.

Conclusion
Hospitalized COVID-19 patients in the U.S. have a high prevalence of myocardial injury, which was associated with poorer survival and outcomes.
Congenital partial pericardial defect discovered incidentally during surgery for lung cancer: a case report and literature review
Authors: Iijima Yoshihito , Ishikawa Masahito , Iwai Shun , Yamagata Aika , Motono Nozomu , Yamagishi Shigeki , Koizumi Kiyoshi , Uramoto Hidetaka 
Published: December 2021

Abstract
Background
Congenital pericardial defects are rare congenital anomalies, often asymptomatic and incidentally detected during thoracic surgery.

Case presentation
A 74-year-old man with primary lung cancer (cT1cN0M0, Stage IA3) underwent thoracoscopic radical lobectomy. At the time of thoracotomy, a pericardial defect was found on the ventral side of the hilar region, and the left atrial appendage was exposed. Due to concern that contact between the bronchial stump and the left atrial appendage may lead to postoperative bleeding and heart hernia, the pericardial defect was closed with an expanded polytetrafluoroethylene GoreTex® membrane. Preoperative computed tomography was reanalyzed with a 1 mm slice, congenital pericardial defect was detected as the pericardium had penetrated under the left atrial appendage.

Conclusions
In congenital partial pericardial defect, contact between the left atrial appendage and bronchial stump, due to movement of the lung or heart, increases the risk of bleeding after lung resection. Therefore, closure of the defect should be considered. Although it is difficult to diagnose congenital partial pericardial defect preoperatively, computed tomography taken with a slice thickness of 1 mm is useful for diagnosis.
LncRNA NEAT1 is upregulated in recurrent aphthous stomatitis (RAS) and has predictive values
Authors: Han Yaolun , Wang Lu , Li Qingfu , Chen Hongli , Ma Xin 
Published: December 2021

Abstract
Background
LncRNA NEAT1 promotes inflammatory responses, which contribute to recurrent aphthous stomatitis (RAS). This study focused on the involvement of NEAT1 in RAS.

Methods
RT-qPCR and ELISA were performed to determine the expression of NEAT1 and proinflammatory factors (IL-2, IL-1β, and TNF-α) in plasma from patients with a history of RAS and showing symptom (n = 80, S-RAS group), people with a history of RAS but showing no symptom (n = 80, NS-RAS group), and controls without a history of RAS (n = 80, Control group). Correlation analysis was performed with Pearson’s correlation coefficient. S-RAS group received treatmen,t and plasma levels of NEAT1 and proinflammatory factors were compared before and after treatment. S-RAS group was followed up for 12 months, and the recurrence was recorded.

Results
Plasma NEAT1, IL-2, IL-1β, and TNF-α levels were the highest in the S-RAS group, followed in turn by NS-RAS and control groups. NEAT1 was positively and significantly correlated with IL-2, IL-1β, and TNF-α across S-RAS and NS-RAS samples, but not control samples. After treatment, plasma levels of NEAT1, IL-2, IL-1β, and TNF-α decreased significantly. Moreover, a higher recurrence rate was observed during the follow-up in patients with high plasma NEAT1 levels.

Conclusion
NEAT1 is upregulated in RAS and correlated with multiple proinflammatory factors. Moreover, NEAT1 has predictive values for RAS.
In vivo and in vitro analysis in a rat model using zoledronate and alendronate medication: microbiological and scanning electron microscopy findings on peri-implant rat tissue
Authors: Kniha Kristian , Buhl Eva Miriam , Möhlhenrich Stephan Christian , Bock Anna , Hölzle Frank , Hellwig Elmar , Al-Ahmad Ali , Modabber Ali 
Published: December 2021

Abstract
Background
The aim of the present study was to assess the development of bacterial deposits and morphological parameters around dental zirconia and titanium implants compared with natural teeth during systemic bisphosphonate medication.

Materials and methods
Fifty-four rats were randomly allocated into one control group and two experimental groups (drug application of zoledronic and alendronic acid), with 18 animals in each group. After 4 weeks of drug delivery, either a zirconia or a titanium implant was immediately inserted. Microbiological analysis conducted 1 week, 8 weeks, and 12 weeks after surgery included total bacterial count and composition measurements. Samples were analyzed in a scanning electron microscope (SEM) equipped with energy-dispersive X-ray spectroscopy (EDX). Bone cell morphology was analyzed by transmission electron microscopy (TEM).

Results
One week after surgery, titanium and zirconia implants of the alendronic acid and control group showed a significantly higher bacterial count when compared to natural teeth in rats with zoledronic acid administration (p < 0.01). Less significant differences were recorded after 3 months, at which time no inter-material differences were evaluated (p > 0.05). I
n the control group, TEM analysis showed that the osteoblasts had a strongly developed endoplasmic reticulum. In contrast, the endoplasmic reticulum of the osteoblasts in drug-treated animals was significantly less developed, indicating less activity.

Conclusions
Within the limits of this study, neither implant material was superior to the other at 3-month follow-up. With regard to the treatment and complications of patients with bisphosphonates, the implant material should not be an influencing factor. Bisphosphonates can be used in the rat model to reduce not only the activity of osteoclasts but also osteoblasts of the peri-implant bone.
Oral administration of tartrazine (E102) accelerates the incidence and the development of 7,12-dimethylbenz(a) anthracene (DMBA)-induced breast cancer in rats
Authors: Zingue Stéphane , Mindang Elisabeth Louise Ndjengue , Awounfack Florence Charline , Kalgonbe Abel Yanfou , Kada Moustapha Mohamet , Njamen Dieudonné , Ndinteh Derek Tantoh 
Published: December 2021

Abstract
Background
Despite the considerable advances made in the treatment of cancer, it remains a global threat. Tartrazine (E102) is a synthetic dye widely used in food industries; it has recently been shown to induce oxidative stress (a well known risk factor of cancer) in rat tissues. The present work therefore aimed to assess the impact of a regular consumption of tartrazine on the incidence of breast cancer in rats.

Methods
Forty (40) Wistar rats aged 55 to 60 days were randomly assigned into 5 groups (n = 8) including two groups serving as normal controls and receiving distilled water (NOR) or tartrazine (NOR + TARZ). The three remaining groups were exposed to the carcinogen DMBA (50 mg/kg) and treated for 20 weeks with either distilled water (DMBA), tartrazine 50 mg/kg (DMBA + TARZ) or a natural dye (DMBA + COL). The parameters evaluated were the incidence, morphology and some biomarkers (CA 15–3, estradiol and α-fetoprotein) of breast cancer. The oxidative status and histomorphology of the tumors were also assessed.

Results
A regular intake of tartrazine led to an early incidence of tumors (100% in rats that received TARZ only vs 80% in rats that received DMBA only), with significantly larger tumors (p < 0.001) (mass = 3500 mg/kg and volume = 4 cm3). The invasive breast carcinoma observed on the histological sections of the animals of the DMBA + TARZ group was more developed than those of the DMBA group. The increase in serum α-fetoprotein (p < 0.05) and CA 15–3 (p < 0.01) levels corroborate the changes observed in tumors. The presence of oxidative activity in animals of the DMBA + TARZ group was confirmed by a significant decrease (p < 0.001) in the activity of antioxidant enzymes (SOD and catalase) as well as the level of GSH and increase in the level of MDA compared to the rats of the DMBA and NOR groups.

Conclusion
Tartrazine therefore appears to be a promoter of DMBA-induced breast tumorigenesis in rats through its oxidative potential. This work encourages further studies on the mechanisms of action of tartrazine (E102) and its limits of use.
Multi-task learning for Chinese clinical named entity recognition with external knowledge
Authors: Cheng Ming , Xiong Shufeng , Li Fei , Liang Pan , Gao Jianbo 
Published: December 2021

Abstract
Background
Named entity recognition (NER) on Chinese electronic medical/healthcare records has attracted significantly attentions as it can be applied to building applications to understand these records. Most previous methods have been purely data-driven, requiring high-quality and large-scale labeled medical data. However, labeled data is expensive to obtain, and these data-driven methods are difficult to handle rare and unseen entities.

Methods
To tackle these problems, this study presents a novel multi-task deep neural network model for Chinese NER in the medical domain. We incorporate dictionary features into neural networks, and a general secondary named entity segmentation is used as auxiliary task to improve the performance of the primary task of named entity recognition.

Results
In order to evaluate the proposed method, we compare it with other currently popular methods, on three benchmark datasets. Two of the datasets are publicly available, and the other one is constructed by us. Experimental results show that the proposed model achieves 91.07% average f-measure on the two public datasets and 87.05% f-measure on private dataset.

Conclusions
The comparison results of different models demonstrated the effectiveness of our model. The proposed model outperformed traditional statistical models.
Severe polymicrobial and fungal periprosthetic osteomyelitis persisting after hip disarticulations treated with caspofungin in risk patients: a case series
Authors: Enz Andreas , Müller Silke , Mittelmeier Wolfram , Klinder Annett 
Published: December 2021

Abstract
Background
Periprosthetic fungal infections are considered rare and opportunistic infections. Treatment is difficult, and established standards do not yet exist. The choice of the appropriate antifungal drug might affect the patient outcome.

Cases
All the three cases presented showed polybacterial recurrent infection of the revision hip arthroplasty. All patients were of younger age, had multiple revisions of the endoprosthesis, each had a large partial femoral replacement greater than 40% of the femoral length, gentamycin-loaded cement, and a long anchoring distance of the used intramedullary stem. Due to the severe life-threatening infection with deep osteomyelitis, an amputation had to be performed. However, despite surgical intervention, the fungal dominated infection persisted. Finally, only the use of caspofungin allowed permanent infection control.

Conclusion
The polybacterial infection is driven by the symbiosis between fungi and bacteria. Therefore, eradication of the fungus is required to achieve elimination of the bacteria. Antimycotics of the echinocandin-class, such as caspofungin, may be considered as initial treatment.
Estimating upper-extremity function from kinematics in stroke patients following goal-oriented computer-based training
Authors: Ballester Belén Rubio , Antenucci Fabrizio , Maier Martina , Coolen Anthony C. C. , Verschure Paul F. M. J. 
Published: December 2021

Abstract
Introduction
After a stroke, a wide range of deficits can occur with varying onset latencies. As a result, assessing impairment and recovery are enormous challenges in neurorehabilitation. Although several clinical scales are generally accepted, they are time-consuming, show high inter-rater variability, have low ecological validity, and are vulnerable to biases introduced by compensatory movements and action modifications. Alternative methods need to be developed for efficient and objective assessment. In this study, we explore the potential of computer-based body tracking systems and classification tools to estimate the motor impairment of the more affected arm in stroke patients.

Methods
We present a method for estimating clinical scores from movement parameters that are extracted from kinematic data recorded during unsupervised computer-based rehabilitation sessions. We identify a number of kinematic descriptors that characterise the patients’ hemiparesis (e.g., movement smoothness, work area), we implement a double-noise model and perform a multivariate regression using clinical data from 98 stroke patients who completed a total of 191 sessions with RGS.

Results
Our results reveal a new digital biomarker of arm function, the Total Goal-Directed Movement (TGDM), which relates to the patients work area during the execution of goal-oriented reaching movements. The model’s performance to estimate FM-UE scores reaches an accuracy of $$R^2$$

R
2

: 0.38 with an error ($$\sigma$$
σ
: 12.8). Next, we evaluate its reliability ($$r=0.89$$

r
=
0.89

for test-retest), longitudinal external validity ($$95\%$$

95
%

true positive rate), sensitivity, and generalisation to other tasks that involve planar reaching movements ($$R^2$$

R
2

: 0.39). The model achieves comparable accuracy also for the Chedoke Arm and Hand Activity Inventory ($$R^2$$

R
2

: 0.40) and Barthel Index ($$R^2$$

R
2

: 0.35).

Conclusions
Our results highlight the clinical value of kinematic data collected during unsupervised goal-oriented motor training with the RGS combined with data science techniques, and provide new insight into factors underlying recovery and its biomarkers.
MycoNews 2021: President’s message, IMA statutes, news, reports, awards, personalia, and book news
Authors: Hawksworth David L. 
Published: December 2021

AbstractThis third annual edition ofMycoNewsstarts with a message from IMA President Wieland Meyer regarding the adoption of new statutes for the IMA, the postponement of IMC12 to 2024, and announcing Marc Stadler as President-elect. The new statutes are included in full. News is provided on the launch of a World Fungus Day, acceptance of the term Funga as an equivalent to Fauna and Flora by the IUCN Species Survival Commission, new arrangements and dates for IMC12 now to be held in Maastricht in July 2024, and revised arrangements for the publication of proposals to change any rules governing the nomenclature of fungi. Reports are provided for IAL9, the symposium of the International Association for Lichenology in Brazil mainly conducted virtually, MycoRise Up! in Poland, and the centenary of the German Mycological Society (DGFM). Birthday greetings from IMA go to David Farr, Marie-Agnés Letrouit-Galinou, Maria Olech, Angela Restrepo, Carol Shearer, James Trappe, and Shun-ichi Udagawa. Tributes are also paid to the passing of the distinguished mycologists Heinz Butin, Karl Esser, Grégoire Hennebert, Jack Rogers, Kálman Vánky, and Bodo Wanke. The contribution concludes with news of seven new mycological books published in 2020–2021, and another forthcoming in 2022.