bluuebunny/crossref_metadata_2025 huggingface dataset:
Dose Escalation Data from the Phase 1 Study of the Liposomal Formulation of Eribulin (E7389-LF) in Japanese Patients with Advanced Solid Tumors
Authors: Sato Jun , Shimizu Toshio , Koyama Takafumi , Iwasa Satoru , Shimomura Akihiko , Kondo Shunsuke , Kitano Shigehisa , Yonemori Kan , Fujiwara Yutaka , Tamura Kenji , Suzuki Takuya , Takase Takao , Nagai Reiko , Yamaguchi Kohei , Semba Taro , Zhao Zi-Ming , Ren Min , Yamamoto Noboru
Published: March 2022

Purpose:

We report the dose-escalation part of a phase I study of liposomal eribulin (E7389-LF) in Japanese patients with advanced solid tumors and no alternative standard therapy.

Patients and Methods:

Patients ≥20 years old were enrolled. E7389-LF doses of 1.0 to 1.5 mg/m2 once every two weeks (Q2W) or 1.0 to 2.5 mg/m2 once every three weeks (Q3W) were planned. The primary objective was to determine the MTD by evaluating dose-limiting toxicities (DLT). Secondary objectives included safety/tolerability assessments, objective response rate (ORR), and progression-free survival; serum biomarker assessment was an exploratory objective.

Results:

Twenty-one patients were enrolled and treated; 12 in the Q3W group (1.0 mg/m2, n = 3; 1.5 mg/m2, n = 3; 2.0 mg/m2, n = 6) and 9 in the Q2W group (1.0 mg/m2, n=3; 1.5 mg/m2, n = 6). The Q3W and Q2W MTDs were 2.0 mg/m2 and 1.5 mg/m2, respectively. One patient receiving 2.0 mg/m2 Q3W had a DLT of grade 3 febrile neutropenia. The most common grade 3 treatment-emergent adverse events were neutropenia (66.7% in Q3W and Q2W) and leukopenia (Q3W, 58.3%; Q2W, 33.3%). One patient in the Q3W group (2.0 mg/m2) and 3 in the Q2W group (1.0 mg/m2, n = 1; 1.5 mg/m2, n = 2) achieved a partial response [overall ORR, 19.0%; 95% confidence interval (CI), 5.4–41.9]. Endothelial [TEK receptor tyrosine kinase (TEK), intercellular adhesion molecule 1 (ICAM1), vascular endothelial growth factor receptor 3 (VEGFR3), platelet/endothelial cell adhesion molecule 1 (PECAM1)], vasculature (collagen IV), and immune-related [interferon gamma (IFNγ), C-X-C motif chemokine ligand 11 (CXCL11), C-X-C motif chemokine ligand 10 (CXCL10)] biomarker levels were increased.

Conclusions:

E7389-LF was well tolerated at 2.0 mg/m2 Q3W and 1.5 mg/m2 Q2W. Considering the toxicity profile of both regimens, the recommended dose was 2.0 mg/m2 Q3W. Expansion cohorts are ongoing.
Gastric Perforation in a 60-Year-Old Woman with CMV Gastritis and Amphetamine Abuse Led to Death
Authors: Khajeh Fatemeh , Safari Fatemeh , Seyyedi Noorossadat , Asadian Fatemeh , Farhadi Ali , Behzad-Behbahani Abbas
Published: March 2022

Gastric perforation as a multi-etiological disease is a full-thickness injury of the stomach wall. In this case report, we presented a 60-year-old woman with a history of suicidal behavior referred to the emergency unit with a decreased level of consciousness due to the multidrug consumption (amphetamine and benzodiazepine). Passing 3 days of admission in the intensive care unit, the patient represented severe abdominal distension, lack of defecation, and the absence of bowel sound, which suggested the gastrointestinal (GI) complication. Abdominal-pelvic sonography followed by laparotomy confirmed the gastric perforation, which finally led to the patient’s death. Pathological analysis showed that the vast involvement of cytomegalovirus (CMV) in the patient’s GI tract resulted in several peptic ulcers. The first report of gastric perforation-related death arises from the partnership of CMV infection and drug poisoning.
Afferent-Loop Syndrome Treated with Endoscopic Ultrasound-Guided Drainage of the Afferent Loop with a Plastic Stent
Authors: Tanikawa Tomohiro , Urata Noriyo , Ishii Katsunori , Katsumata Ryo , Nishino Ken , Suehiro Mitsuhiko , Kawanaka Miwa , Haruma Ken , Kawamoto Hirofumi
Published: March 2022

Afferent-loop syndrome (ALS) is known as a rare complication of partial or total gastrectomy and also occurs after pancreatoduodenectomy. The symptoms of ALS vary with the location of the mechanical obstruction, and the choice of therapeutic method should reflect the patient’s condition and disease state. Herein, we report the use of endoscopic ultrasound (EUS)-guided afferent loop drainage with a plastic stent and its reintervention for malignant ALS. An 80-year-old man was admitted to our hospital with abdominal pain. Thirty-two months before, the patient underwent left hepatectomy with choledochojejunostomy and Roux-en-Y reconstruction for hilar biliary adenocarcinoma. An abdominal CT scan showed a dilated afferent loop and a low-density lesion in the peritoneum that suggested recurrence of hilar biliary adenocarcinoma and malignant ALS due to mechanical obstruction of the afferent loop caused by peritoneal dissemination. The recurrence site did not include the choledochojejunostomy anastomosis and was far distal to it. We employed a convex EUS scope and directly punctured the afferent loop from the stomach. We inserted one double pig-tail stent, and the ALS immediately improved. Five months later, ALS recurred, and we exchanged a plastic stent through the fistula. After reintervention, ALS did not recur before the patient’s death due to cancer progression.
Em busca do gesto espontâneo: a subjetivação da mulher negra em A cor púrpura, de Alice Walker
Authors: Almeida Natália de Sousa , Marques Rodrigo Vieira
Published: March 2022

Partindo do diálogo entre literatura e psicanálise, este artigo visa apresentar uma possível leitura do romance A cor púrpura, de Alice Walker, segundo a teoria winnicottiana do amadurecimento. Neste romance, Walker apresenta a triste história de Celie, uma jovem negra arrancada violentamente do convívio de seus filhos e de sua irmã. Casada com um homem violento, Celie vive como se não tivesse existência. O ambiente opressor e violento descrito por Walker ilustra bem as falhas ambientais que Winnicott considera presentes na constituição do falso self. Em contrapartida, a construção do verdadeiro self, caracterizado pela criatividade e pelo “gesto espontâneo”, pressupõe um processo de subjetivação marcado por uma experiência afetiva e “suficientemente boa” da alteridade. Neste sentido, é possível compreender as transformações vividas por Celie em seu encontro com Shug Avery, de modo a vivenciar a sua própria feminilidade. A experiência do encontro humano possibilita processos de ressignificação e de elaboração das falhas ambientais, por conseguinte, processos de desenvolvimento emocional. Neste romance, o tempo da narrativa revela o tempo do amadurecimento humano, destacando-se, ao lado da crítica social, a relação dos componentes masculinos e femininos que integram o ser e o fazer como dimensões fundamentais e constitutivas do self.
O ensino da leitura literária na escola básica: perspectivas e desafios a partir da BNCC
Authors: Portolomeos Andrea , Nepomuceno Susana Vieira Rismo
Published: March 2022

Antonio Candido, no texto O direito à literatura, defende que a leitura do texto literário promove uma experiência humanizadora à medida que o indivíduo tende a se tornar mais empático diante das mais diferentes realidades. A Base Nacional Comum Curricular (BNCC) é homologada em 2017, oferecendo aos professores da educação básica orientações que dialogam com o posicionamento de Candido. Todavia, entra em contradição em suas diretrizes, se distanciando da compreensão do texto literário enquanto material estético. Assim, este artigo promove uma discussão sobre a especificidade do texto e da leitura literária que auxilie o professor na sua prática de sala de aula e ainda reflete sobre as perspectivas e desafios presentes na BNCC no que se refere ao ensino da leitura literária como forma de promover aulas de literatura mais emancipadoras.
Mobile Stroke Units: Evidence, Gaps, and Next Steps
Authors: Navi Babak B. , Audebert Heinrich J. , Alexandrov Anne W. , Cadilhac Dominique A. , Grotta James C. ,   on behalf of the PRESTO (Prehospital Stroke Treatment Organization) Writing Group
Published: March 2022

Mobile stroke units (MSUs) are specialized ambulances equipped with the personnel, equipment, and imaging capability to diagnose and treat acute stroke in the prehospital setting. Over the past decade, MSUs have proliferated throughout the world, particularly in European and US cities, culminating in the formation of an international consortium. Randomized trials have demonstrated that MSUs increase stroke thrombolysis rates and reduce onset-to-treatment times but until recently it was uncertain if these advantages would translate into better patient outcomes. In 2021, 2 pivotal, large, controlled clinical trials, B_PROUD and BEST-MSU, demonstrated that as compared with conventional emergency care, treatment aboard MSUs was safe and led to improved functional outcomes in patients with stroke. Further, the observed benefit of MSUs appeared to be primarily driven by the higher frequency of ultra-early thrombolysis within the golden hour. Nevertheless, questions remain regarding the cost-effectiveness of MSUs, their utility in nonurban settings, and optimal infrastructure. In addition, in much of the world, MSUs are currently not reimbursed by insurers nor accepted as standard care by regulatory bodies. As MSUs are now established as one of the few proven acute stroke interventions with an effect size that is comparable to that of intravenous thrombolysis and stroke units, stroke leaders and organizations should work with emergency medical services, governments, and community stakeholders to determine how MSUs might benefit individual communities, and their optimal organization and financing. Future research to explore the effect of MSUs on intracranial hemorrhage and thrombectomy outcomes, cost-effectiveness, and novel models including the use of rendezvous transports, helicopters, and advanced neuroimaging is ongoing. Recommended next steps for MSUs include reimbursement by insurers, integration with ambulance networks, recognition by program accreditors, and inclusion in registries that monitor care quality.
When Work Moves: Job Suburbanization and Black Employment
Authors: Miller Conrad
Published: March 2022

This paper examines whether job suburbanization caused declines in black employment rates from 1970 to 2000. I find that black workers are less likely than white workers to work in observably similar jobs that are located further from the central city. Using evidence from establishment relocations, I find that this relationship reflects at least in part the causal effect of job location. At the local labor market level, I find that job suburbanization is associated with substantial declines in black employment rates relative to white employment rates. Evidence from nationally planned highway infrastructure corroborates a causal interpretation.
Strategic or Confused Firms? Evidence from “Missing” Transactions in Uganda
Authors: Almunia Miguel , Hjort Jonas , Knebelmann Justine , Tian Lin
Published: March 2022

Are firms sophisticated maximizers, or do they appear to make mistakes? Using transaction data from Ugandan value-added tax returns, we show that sellers and buyers report different amounts 79% of the time, despite invoices being easily cross-checked. Our estimates suggest that most firms are “advantageous misreporters,” but that 25% are “disadvantageous misreporters” who systematically overreport own sales minus purchases such that their tax liability increases. Similarly, many firms—especially disadvantageous misreporters—fail to VAT-report imported inputs they themselves reported at Customs, increasing their liability. On net, unilateral VAT misreporting cost Uganda about US$384 million in foregone 2013–2016 tax revenue.
A New and Simple Frequency Quadrupling Millimeter-Wave Signal Generation Enabled by a Single Mach-Zehnder Modulator Without Optical Filter
Authors: Wang Dong-Fei , Hui Shi-Hao , Ding Hai-Yang , Li Zi-Chen , Li Zhen-Zhen , Sun De-Zhi
Published: March 2022

In this work, we have designed and proposed a new optical method to realize the generating of frequency quadrupling millimeter-wave (mm-wave) only employing one Mach-Zehnder modulator (MZM), and no any optical filter is needed. Compared with the previously reported quadruple frequency
scheme, this work greatly simplifies the structure of the system, and makes the performance better and the cost lower. In the scheme, the MZM is operated at peak bias point, which is applied to retain the even order optical sidebands and wipe off the odd order optical harmonics. By tuning-up
the optical shifter and optical attenuator (OATT) to control the zeroth order optical carrier returns zero, only ±2nd order optical tones are generated. We demonstrated and discussed the presented scheme feasibility based on the detailed mathematical formula derivation and numerical
simulation, the simulation results of which show that employing a sinusoidal radio frequency (RF) source with frequency at 10 GHz to drive a push-pull MZM, a 40 GHz millimeter-wave (mm-wave) signal can be obtained. In the work, the performance of the generated quadrupling signal is that the
optical sideband suppression ratio (OSSR) is 34.8 dB and the radio frequency sideband suppression ratio (RFSSR) can reach 27.2 dB.
Simulation Engineering in Quantum Dots for Efficient Photovoltaic Solar Cell Using Copper Iodide as Hole Transport Layer
Authors: Tiwari Rashmi , Sadanand  , Dubey Priyanka , Lohia Pooja , Dwivedi D. K. , Fouad Hassan , Akhtar M. S.
Published: March 2022

Among the third-generation solar cells, quantum dot solar cell is attracting the researchers and the widespread research has been increasing day by day. It has appropriate electrical and optical properties for a photovoltaic response. Quantum dot has a tunable band gap and its size
is less than the Bohr exciton radius. In this work, copper iodide (CuI) is the hole transport layer (HTL), the absorber layer is tetrabutylammonium iodide treated lead sulphide (PbS-TBAI), and titanium dioxide (TiO2) is the electron transport layer (ETL). The device has been rectified
to obtain maximum efficiency followed by device optimization. The variation of thickness of the ETL, HTL and absorber layer has been done to optimize the performance of the proposed device. Further, variation of doping density of HTL and interface defect density (IDD) of HTL/PbS-TBAI and PbS-TBAI/ETL
has been done to overall optimize the device performance. The interface defect density at both the interfaces (HTL/PbS-TBAI and PbS-TBAI/ETL) has been varied from 1×1010 cm−2 to 1×1017 cm−2 without changing the rest of the
device parameters. The result shows notable, diminution in the photo-voltaic performance of the solar cell at higher interface defect density. Quantum efficiency (Q.E) and J-V curve have been investigated. From this study, we have observed that the simulated device structure could be used
as an efficient solar cell.
Accurate and Efficient Calculation Method for Ion Flow Field Near Direct Current Voltage Divider
Authors: Xiu Liancheng , Du Zhiye , Jin Qi , Cai Hongwei , He Jingxuan
Published: March 2022

The surface of grading rings in DC voltage divider may cause surface wear or scratch, resulting in corona phenomenon. Due to the influence of space charges and surface charges, the total electric field near DC voltage divider is different from the nominal electric field. For the problem
of solving the ion-flow field near the DC voltage divider, this paper proposes an improved method based on upwind Finite Element Method (FEM). According to the nominal electric field results, the updated switch state of the charge density is determined, and then the upwind FEM is used to update
the node charge density. This method uses a dual-scene iterative method to converge for the multiple grading rings, which improves the convergence. The correctness of the method is verified by the coaxial cylindrical electrode. Finally, the ion-flow field near 500 kV DC voltage divider is
calculated. The results show that the total electric field near the grading ring becomes more uniform due to the effect of space charges and surface charges. In the space far from or close to the grading rings, the total electric field will increase or decrease compared with the nominal electric
field. The method in this paper provides guidance for the calculation of the ion-flow field near the DC divider and its insulation design.
Short-Term Solar Power Forecasting and Uncertainty Analysis Using Long and Short-Term Memory
Authors: Zhang Wei
Published: March 2022

As a green and renewable resource, the scale of solar energy is increasing. Huge amount of solar energy penetration in a distribution system causes drastic changes in the load forming a duck shape load curve which may cause stability problems. Accurate load forecasting and demand response
procedures are the key tasks of power distribution system management. For this reason, this paper proposes a new mechanism for optimized operation of solar microgrid based on deep learning long and short-term memory (LSTM) and demand response (DR). LSTM is used for load prediction, and linear
integer programming is used to implement load scheduling. The proposed DR procedure is used for load management, the proposed method is implemented in a modified IEEE-12 bus radial distribution network. In a dynamic pricing environment, not only the stability of the voltage is guaranteed,
but the electricity cost is minimized. This paper solves the dual objectives that is flattening the duck curve and electricity cost minimization.
Energetics and Mixing of Stratified, Rotating Flow over Abyssal Hills
Authors: Zemskova Varvara E. , Grisouard Nicolas
Published: March 2022

One of the proposed mechanisms for energy loss in the ocean is through dissipation of internal waves, in particular above rough topography where internal lee waves are generated. Rates of dissipation and diapycnal mixing are often estimated using linear internal wave generation theory and a constant value for mixing efficiency. However, previous oceanographic measurements found that nonlinear dynamics may be important close to topography. To investigate the role of nonlinear interactions, we conduct idealized 3D direct numerical simulations (DNS) of steady flow over 1D topography and vary the topographic height, which correlates to the degree of flow nonlinearity. We analyze the spatial distribution of energy transfer rates between internal waves and the nongeostrophic portion of the time-mean flow, and of dissipation and diapycnal mixing rates. In our simulations with taller, more nonlinear topographies, energy transfer rates are similar to previously unexplained oceanographic observations near topography: internal waves gain energy from time-mean flow through horizontal straining and lose energy through vertical shearing. In the tall topography simulations, buoyancy fluxes also play a significant role, consistent with observations but contrary to linear wave theory, suggesting that quasigeostrophy-based approximations and linear theory may not hold in some regions above rough topography. Both dissipation and mixing rates increase with topographic height, but their vertical distributions differ between topographic regimes. As such, the vertical profile of mixing efficiency is different for linear and nonlinear topographic regimes, which may need to be incorporated into parameterizations of small-scale processes in models and estimates of ocean energy loss.
Economic Viability and Emissions of Multimodal Transportation Infrastructure in a Changing Arctic
Authors: Goldstein Michael A. , Lynch Amanda H. , Yan Ruitian , Veland Siri , Talleri William
Published: March 2022

As Arctic open water increases, shipping activity to and from mid- and western Russian Arctic ports to points south has notably increased. A number of Arctic municipalities hope increased vessel traffic will create opportunities to become a major transshipment hub. However, even with more traffic passing these ports, it might still be economically cheaper to offload cargo at a more southern port, which may also result in lower emissions. Ultimately, the question of whether to use a transshipment in the Arctic versus an established major European port is determined by the relative costs (or emissions) of sea versus land travel. This study calculates the relative competitiveness of six Norwegian coastal cities as multimodal hubs for shipments. We quantify the relative prices and CO2 emissions for sea and land travel for routes starting at the Norwegian–Russian sea border with an ultimate destination in central Europe and find that all existing routes are not competitive with routes using the major existing Port of Rotterdam (Netherlands); even with investments in port expansion and modernization, they would be underutilized regardless of an increase in vessel traffic destined for central Europe. We then examine under what relative prices (emissions) these routes become economically viable or result in lower emissions than using existing southern ports. Notably, the cheapest routes generally produce the lowest emissions, and the most expensive routes tend to have the largest emissions. Communities should consider relative competitiveness prior to making large infrastructure investments. While some choices are physically possible, they may not be economically viable.

Significance Statement

Climate change, while disruptive, can also create new opportunities. Many Arctic cities hope to become a major transshipping hub as declining sea ice opens new shipping routes from western and mid-Russian Arctic ports to European ports. This paper quantifies the relative competitiveness of six Norwegian coastal cities as multimodal transportation hubs and finds that they are uncompetitive with the more southern port in Rotterdam (Netherlands). We also show that the most economically competitive routes have lower direct emissions. Thus, while Arctic ports provide critical services in support of local and regional economic activity, even with year-round Arctic navigation Arctic ports’ development into major transshipment hubs for cargo destined for more distant locations may be neither economically viable nor desirable.
Cytological diagnosis of microfilaria coexistent with suspected malignancy of breast and ovary in a young pregnant female
Authors: Singh Sunita , Gill Meenu , Dalal Niti , Gupta Veena , Jain Promil , Gupta Sumiti
Published: March 2022

Filariasis is a major health issue of tropical and subtropical regions and is endemic in India. It is rarely seen in cytological smears, exfoliative scrapings or in effusions. We present the case of a 29-year old female with filaria found on cytological examination of both breast and ovary.
Learning About Communication Disorders: Comparison of Two Instructional Methods With Multimedia for Preservice Teachers
Authors: Allen Abigail A.
Published: March 2022

Content acquisition podcasts (CAPs) are a popular tool in special educator preparation but little is known about their application to communication disorders. This quasi-experimental study investigated the effectiveness of two instructional methods: lecture plus video and a content acquisition podcast (CAP). Participants were undergraduates in early childhood education and special education programs ( N = 62). Participants were assessed on their knowledge and application of communication development and disorders at four time points. Results indicated that the lecture plus video condition was more effective at producing knowledge gains compared to the CAP condition, but both conditions were equally effective at producing gains in application ability at post-test. Neither group maintained their knowledge gains 8 weeks after instruction. Learning condition did not affect participants in the two education programs differently. Implications for teacher preparation are discussed.
Towards recycling of challenging waste fractions: Identifying flame retardants in plastics with optical spectroscopic techniques
Authors: Sormunen Tuomas , Uusitalo Sanna , Lindström Hannu , Immonen Kirsi , Mannila Juha , Paaso Janne , Järvinen Sari
Published: March 2022

The use of plastics is rapidly rising around the world causing a major challenge for recycling. Lately, a lot of emphasis has been put on recycling of packaging plastics, but, in addition, there are high volume domains with low recycling rate such as automotive, building and construction, and electric and electronic equipment. Waste plastics from these domains often contain additives that restrict their recycling due to the hazardousness and challenges they bring to chemical and mechanical recycling. As such, the first step for enabling the reuse of these fractions is the identification of these additives in the waste plastics. This study compares the ability of different optical spectroscopy technologies to detect two different plastic additives, fire retardants ammonium polyphosphate and aluminium trihydrate, inside polypropylene plastic matrix. The detection techniques near-infrared (NIR), Fourier-transform infrared (FTIR) and Raman spectroscopy as well as hyperspectral imaging (HSI) in the short-wavelength infrared (SWIR) and mid-wavelength infrared (MWIR) range were evaluated. The results indicate that Raman, NIR and SWIR HSI have the potential to detect these additives inside the plastic matrix even at relatively low concentrations. As such, utilising these methods has the possibility to facilitate sorting and recycling of as of yet unused plastic waste streams, although more research is needed in applying them in actual waste sorting facilities.
Optimization of low-thrust multi-debris removal mission via an efficient approximation model of orbit rendezvous
Authors: Huang An-yi , Luo Ya-zhong , Li Heng-nian , Wu Sheng-gang
Published: March 2022

An efficient iterative approximation model for low-thrust rendezvous in low-earth orbit is proposed to be applied in optimization of multi-debris removal missions. Based on an existing method for impulsive orbit rendezvous and a novel iteration process, the propellant cost and thrust time of a low-thrust rendezvous can be quickly evaluated. Moreover, another iterative method is also designed to help find the minimal transfer duration required for orbit rendezvous. Then, its application in the max-reward optimization of debris removal mission with a large-scale targets to be selected is studied. In the three-steps optimization including target selection, sequence optimization, and low-thrust trajectory optimization, the iterative approximation model is used to deal with the constraints and evaluate the objective functions more efficiently. The problem of the eighth Chinese trajectory optimization competition was used to test the performance, and a leading solution including 93 targets was found. Comparisons with previous results were made to prove the advantages of the method in this paper.
Pure bending of an elastic prismatic beam made of a material with density-dependent material parameters
Authors: Průša Vít , Rajagopal Kumbakonam Ramamani , Wineman Alan
Published: March 2022

We investigate the pure bending of an elastic prismatic beam, but unlike in the classical setting we assume that the material parameters are density-dependent. The corresponding boundary value problem admits a semi-analytical solution, and the derived formulae allow one to quickly assess the impact of density-dependent material parameters on the predicted deformation across various parameter regimes, and consequently make a decision on the importance of the density-dependent material parameters in the given setting.
Angioplasty And stenting For symptomatic intracranial atherosclerotic disease: How I Do It
Authors: Mekonnen Ermias A. , Tekle Wondwossen G. , Desai Sohum K. , Hassan Ameer E.
Published: March 2022

Intracranial atherosclerotic disease (ICAD) is a common cause of acute ischemic stroke. ICAD has a high rate of recurrent ischemic stroke despite recommended adequate medical treatment. Endovascular treatment of ICAD has been controversial due to high periprocedural complication in historic randomized clinical trials (RCTs). Recently, a multicenter prospective study of stent placement in patients with high grade intracranial stenosis that evaluated safety and efficacy of Balloon-mounted stents (BMS) in symptomatic ICAD showed low rates of periprocedural stroke (5.6%) than the SAMMPRIS (14.7%) and VISSIT (21.4%) trials. This review highlights the recent evolution of endovascular therapy for symptomatic ICAD.
Real-world multicentre analysis of neoadjuvant immunotherapy and chemotherapy in localized or oligometastatic non-small cell lung cancer (KOMPASSneoOP)
Authors: Faehling Martin , Witte Hanno , Sebastian Martin , Ulmer Matthias , Sätzler Rainer , Steinestel Konrad , Brückl Wolfgang M. , Evers Georg , Büschenfelde Christian Meyer zum , Bleckmann Annalen
Published: March 2022

Background:

Recent clinical trials demonstrate the feasibility of neoadjuvant immuno(chemo)therapy and report high rates of pathological remission, a surrogate marker for overall survival.

Patients and methods:

This is a retrospective multicentre real-world analysis of patients with locally resectable NSCLC, including oligometastatic disease, who received neoadjuvant immuno(chemo)therapy and resection. Consolidating immunotherapy was applied following multidisciplinary board recommendation. Primary endpoint was the rate of complete pathological response (pCR, no residual vital tumour cells) or major pathological response (MPR, ⩽ 10% residual vital tumour cells). Secondary endpoints included the radiological response and survival.

Results:

Seven centres contributed 59 patients (56% stage IIB–IIIC, 44% in stage IVA–IVB with up to four oligometastatic sites). MPR was found in 68% including 53% with pCR. There were no radiological progressions. Median follow-up was 24.3 months. At 12 and 24 months, progression-free survival was 82.6% and 68.1%, and overall survival was 89.5% and 87.2%, respectively.

Conclusion:

To our knowledge, this study encompassed the largest NSCLC real-world cohort treated with neoadjuvant immuno(chemo)therapy to date. In routine clinical practice, resection after neoadjuvant immuno(chemo)therapy is feasible in patients with locally resectable NSCLC, including oligometastatic disease. In line with clinical trials, we found MPR in more than two-thirds of patients. Early data show encouraging survival.
Associated risk factor of tuberculosis infection among adult patients in Gedeo Zone, Southern Ethiopia
Authors: Diriba Kuma , Awulachew Ephrem
Published: March 2022

Background:

Tuberculosis remains a major global health problem causing death among millions of people each year. Even though many of the World Health Organization recommended tuberculosis control strategies were implemented, there is still a major gap in tuberculosis case detection and treatment which resulted in rapid transmission of the cases in high burden countries. This study aimed to provide updated information on the contributing factors for the development of tuberculosis.

Methods:

A case–control study was carried out in Gedeo Zone from February to July 2021 to assess the risk factors of tuberculosis. Cases were confirmed pulmonary tuberculosis patients with age ⩾18 years, while controls were participants who were confirmed to be pulmonary tuberculosis negative with the same age. Multivariate logistic regression models were used to assess the associated risk factor.

Results:

A total of 368 individuals (173 cases and 173 controls) were included in this study. Based on the multivariable logistic regression analysis, we identified six variables as independent risk factors for the development of tuberculosis after controlling possible confounders. Those were patients with income <1500 Ethiopian birr per month (adjusted odds ratio = 2.35; 95% confidence interval: 1.22–3.97), patients with no educational background (illiterate) (adjusted odds ratio = 2.10; 95% confidence interval: 1.17–2.51), patients smoking cigarette (adjusted odds ratio = 2.89; 95% confidence interval: 2.10–3.82), patients chewing khat (adjusted odds ratio = 2.86; 95% confidence interval: 1.28–3.79), patients in close contact with known tuberculosis cases (adjusted odds ratio = 3.63; 95% confidence interval: 2.24–4.46), and patients being positive for HIV (adjusted odds ratio = 3.01; 95% confidence interval: 1.07–3.52) who were found to be significantly associated with tuberculosis development, while Bacille Calmette-Guérin vaccination had a protective effect against the development of tuberculosis (adjusted odds ratio = 0.52; 95% confidence interval: 0.21–0.88).

Conclusion:

The priority should be given to the identified contributing factors through application of coordinated efforts on screening of patients suspected for pulmonary tuberculosis and all contacts of pulmonary tuberculosis patients and treatment of known tuberculosis cases, and appropriate control methods to reduce Mycobacterium tuberculosis cases.
A Preliminary Study on Self-Healing and Self-Health Management in Older Adults: Perspectives From Healthcare Professionals and Older Adults in Taiwan
Authors: Chu Kuei-Hui , Tung Heng-Hsin , Clinciu Daniel L , Hsu Hua-I , Wu Yi-Chen , Hsu Ching-I , Lin Shu-Wei , Pan Shi-Jun
Published: March 2022

The human body has tremendous self-healing capacity and regeneration after injuries and pathogen invasions. These factors are particularly important in older adults which take longer to heal and recover physically. In addition to clinical investigations, perspectives from both experts in the field and the living experiences of the general public could play significant roles to enhance the body’s healing mechanisms in older adults. A semi-structured interview was conducted which included 15 participants (9 experts and 6 older adults aged 65 years and older). Content analysis with an inductive approach was employed about participants’ experiences and perspectives. All participants in this study revealed that self-healing mechanisms can be enhanced through physiological, psychological, and socio-environmental factors. When more of these factors can be integrated into a recovery management plan, it can hasten self-healing in older adults. Social capability has a profound impact on an individual’s mental health while oral health and hygiene significantly affect the nutritional intake status. In regards to physical aspects, regular daily activity patterns, nutritious eating, moderate exercise, and sleep quality are significant, while psychological aspects such as cheerfulness, positive attitudes, and good interpersonal relationships can help control chronic diseases.
Long-term follow-up for the development of subsequent malignancies in patients treated with genetically modified IECs
Authors: Steffin David H. M. , Muhsen Ibrahim N. , Hill LaQuisa C. , Ramos Carlos A. , Ahmed Nabil , Hegde Meenakshi , Wang Tao , Wu Mengfen , Gottschalk Stephen , Whittle Sarah B. , Lulla Premal D. , Mamonkin Maksim , Omer Bilal , Rouce Rayne H. , Heczey Andras , Metelitsa Leonid S. , Grilley Bambi J. , Robertson Catherine , Torrano Virginia , Lapteva Natalia , Gee Adrian P. , Rooney Cliona M. , Brenner Malcolm K. , Heslop Helen E.
Published: March 2022

Subsequent malignancies are well-documented complications in long-term follow-up of cancer patients. Recently, genetically modified immune effector (IE) cells have shown benefit in hematologic malignancies and are being evaluated in clinical trials for solid tumors. Although the short-term complications of IE cells are well described, there is limited literature summarizing long-term follow-up, including subsequent malignancies. We retrospectively reviewed data from 340 patients treated across 27 investigator-initiated pediatric and adult clinical trials at our center. All patients received IE cells genetically modified with γ-retroviral vectors to treat relapsed and/or refractory hematologic or solid malignancies. In a cumulative 1027 years of long-term follow-up, 13 patients (3.8%) developed another cancer with a total of 16 events (4 hematologic malignancies and 12 solid tumors). The 5-year cumulative incidence of a first subsequent malignancy in the recipients of genetically modified IE cells was 3.6% (95% confidence interval, 1.8% to 6.4%). For 11 of the 16 subsequent tumors, biopsies were available, and no sample was transgene positive by polymerase chain reaction. Replication-competent retrovirus testing of peripheral blood mononuclear cells was negative in the 13 patients with subsequent malignancies tested. Rates of subsequent malignancy were low and comparable to standard chemotherapy. These results suggest that the administration of IE cells genetically modified with γ retroviral vectors does not increase the risk for subsequent malignancy.
Effects of subchronic exposure of nonylphenol on the expression of immune-related factors and estrogen receptors in the spleen of rats
Authors: Fu Xiangjun , Xu Jie , Ni Chengyu , Yu Degang , Wang Haibo , Wang Pan , Luo Man , Yu Jie
Published: March 2022

Background

Previous studies have shown that EDCs may activate nuclear transcription factor, such as activator protein-1 (AP-1), nuclear factor of activated Tcells (NF-AT) and nuclear factor kappa B (NF-κB) in the process of immune damage. At the same time, some experts believed that estrogen may play an important role in this process. As a typical representative of EDCs, nonylphenol (NP) has not been reported. The aim of this work was to explore the relationship between the immune inflammatory damage and the changes in estrogen expression in male rats during the chronic exposure to NP at environmental concentrations. Sixty SPF Sprague–Dawley rats were divided into five groups (n = 12 per group): blank control group (corn oil), low-dose NP exposure group (0.4 mg/kg/d), medium-dose NP exposure group (4 mg/kg/d), high-dose NP exposure group (40 mg/kg/d), and estradiol control group (E2: 30 μg/kg/d).

Results

Compared with the control group, rat spleen organ coefficient, number of spleen nodules, relative area of lymph nodes and white pulp were relatively reduced in the L (NP, 0.4 mg/kg) and H (NP, 40 mg/kg) exposure dose groups (P < 0.001). Lymphocytes were rich in cytoplasm, mitochondria were swollen, part of the cristae was reduced, and rough endoplasmic reticulum was expanded. The serum levels of IgG (P < 0.001) and IgM (P = 0.002) showed a downward trend. The percentage of Th cells (CD3+CD4+) was significantly decreased (P < 0.001), and the percentage of B lymphocytes shows an opposite trend (P < 0.001). Giemsa staining showed that the number of neutrophils (P < 0.001) was increased. The expressions of estrogen receptor ER-α and ER-β protein in the spleen increased significantly (P < 0.001). The expressions of AP-1 protein and NF-AT protein in the spleen were increased, and the expression of NF-KB protein was decreased (P < 0.001). The expressions of IL-4, ER-α and ER-β (P < 0.001) levels in serum increased. The mRNA-seq bioinformatics detection showed the final differentially expressed immune-inflammatory-related genes between the control and H-NP groups as follow: down-regulated: TLR4, Gata3, IL12, up-regulated: TNF-a, IL10, INOS. The mRNA expressions of ER-α, ER-β, NF-KB, IL4, AP-1, TLR4, Gata3, and NF-AT were consistent with the results of mRNA-seq analysis. NP content was correlated with the expressions of ER-α, ER-β, IL4, AP-1, NF-AT, TLR4, NF-KB, as well as IL-12 proteins in the spleen tissue ([r] < 1,P < 0.05).

Conclusions

Chronic exposure to NP at environmental concentration could cause immune dysfunction, resulting in immunotoxicity and inflammatory effects, and lead to changes in the activity of transcription factors and differential immune inflammatory factors in rats.

Graphical Abstract
Genome-wide identification and comparative analysis of the PYL gene family in eight Rosaceae species and expression analysis of seeds germination in pear
Authors: Wang Guoming , Qi Kaijie , Gao Xin , Guo Lei , Cao Peng , Li Qionghou , Qiao Xin , Gu Chao , Zhang Shaoling
Published: March 2022

Abscisic acid (ABA) is a phytohormone that plays important roles in the regulation of plant growth, seed germination, and stress responses. The pyrabactin resistance 1-like (PYR/PYL) protein, an ABA receptor, was involved in the initial step in ABA signal transduction. However, the evolutionary history and characteristics of PYL genes expression remain unclear in Chinese white pear (Pyrus bretschneideri) or other Rosaceae species. In this study, 67 PYL genes were identified in eight Rosaceae species, and have been classified into three subgroups based on specific motifs and phylogenetic analysis. Intriguingly, we observed that whole-genome duplication (WGD) and dispersed duplication (DSD) have a major contribution to PYL family expansion. Purifying selection was the major force in PYL genes evolution. Expression analysis finds that PYL genes may function in multiple pear tissues. qRT-PCR validation of 11 PbrPYL genes indicates their roles in seed germination and abiotic stress responses. Our study provides a basis for further elucidation of the function of PYL genes and analysis of their expansion, evolution and expression patterns, which helps to understand the molecular mechanism of pear response to seed germination and seedling abiotic stress.
Changes in gene body methylation do not correlate with changes in gene expression in Anthozoa or Hexapoda
Authors: Dixon Groves , Matz Mikhail
Published: March 2022

Background

As human activity alters the planet, there is a pressing need to understand how organisms adapt to environmental change. Of growing interest in this area is the role of epigenetic modifications, such as DNA methylation, in tailoring gene expression to fit novel conditions. Here, we reanalyzed nine invertebrate (Anthozoa and Hexapoda) datasets to validate a key prediction of this hypothesis: changes in DNA methylation in response to some condition correlate with changes in gene expression.

Results

In accord with previous observations, baseline levels of gene body methylation (GBM) positively correlated with transcription, and negatively correlated with transcriptional variation between conditions. Correlations between changes in GBM and transcription, however, were negligible. There was also no consistent negative correlation between methylation and transcription at the level of gene body methylation class (either highly- or lowly-methylated), anticipated under the previously described “seesaw hypothesis”.

Conclusion

Our results do not support the direct involvement of GBM in regulating dynamic transcriptional responses in invertebrates. If changes in DNA methylation regulate invertebrate transcription, the mechanism must involve additional factors or regulatory influences.
Strain-based discoordination imaging during exercise in heart failure with reduced ejection fraction: Feasibility and reproducibility
Authors: Fixsen Louis S. , Wouters Philippe C. , Lopata Richard G. P. , Kemps Hareld M. C.
Published: March 2022

Purpose

Various parameters of mechanical dyssynchrony have been proposed to improve patient selection criteria for cardiac resynchronization therapy, but sensitivity and specificity are lacking. However, echocardiographic parameters are consistently investigated at rest, whereas heart failure (HF) symptoms predominately manifest during submaximal exertion. Although strain-based predictors of response are promising, feasibility and reproducibility during exercise has yet to be demonstrated.

Methods

Speckle-tracking echocardiography was performed in patients with HF at two separate visits. Echocardiography was performed at rest, during various exercise intensity levels, and during recovery from exercise. Systolic rebound stretch of the septum (SRSsept), systolic shortening, and septal discoordination index (SDI) were calculated.

Results

Echocardiography was feasible in about 70–80% of all examinations performed during exercise. Of these acquired views, 84% of the cine-loops were suitable for analysis of strain-based mechanical dyssynchrony. Test–retest variability and intra- and inter-operator reproducibility at 30% and 60% of the ventilatory threshold (VT) were about 2.5%. SDI improved in the majority of patients at 30% and 60% of the VT, with moderate to good agreement between both intensity levels.

Conclusion

Although various challenges remain, exercise echocardiography with strain analysis appears to be feasible in the majority of patients with dyssynchronous heart failure. Inter- and intra-observer agreement of SRSsept and SDI up to 60% of the VT were comparable to resting values. During exercise, the extent of SDI was variable, suggesting a heterogeneous response to exercise. Further research is warranted to establish its clinical significance.
The clinical applicability of percutaneous splenic vein stent implantation for pancreatic portal hypertension
Authors: Liu Jingjing , Wang Qingbing , Ding Xiaoyi , Liu Qin , Huang Wei , Gu Junwei , Wang Zhongmin , Wu Wei , Wu Zhiyuan
Published: March 2022

Background

Pancreatic portal hypertension (PPH) is a type of extrahepatic portal hypertension. We compared the clinical efficacy of different treatment methods for PPH caused by splenic vein stenosis in chronic pancreatitis.

Methods

This article retrospectively analyzed the PPH cases that were caused by splenic vein stenosis after chronic pancreatitis. Patients were divided into three groups according to the different treatments: splenic vein stent implantation (stent group), splenectomy, and only medications (conservative group). The treatment effects from each group were compared.

Results

A total of 33 patients were retrospectively analyzed in this study (9, 12, and 12 patients in each group respectively). All the procedures were successful in the stent and splenectomy groups. During the follow-up, no patient had gastrointestinal bleeding recurrence in the stent and splenectomy groups. However, in the conservative group, the incidence of portal hypertensive gastropathy and upper gastrointestinal bleeding were 50% and 25%. In the stent group, all the varicose veins at the base of the stomach had shrunk by varying degrees, and the red color signs regressed. The stent patency rate was 100%. No major complication occurred. The average platelet count at 1, 3, 6-months postoperatively were all significantly higher than the preoperative value (P < 0.05). The average postoperative hospital stay duration was significantly shorter than that of the splenectomy group (3.1 ± 1.4 days vs. 16.1 ± 8.1 days; P < 0.05). In the splenectomy group, postoperative fever occurred in 4 patients. Postoperative infection occurred in 2 patients (one with abdominal cavity infection and the other with incision infection). Delayed abdominal bleeding occurred in one patient. Portal vein thrombosis occurred in 2 patients during follow up.

Conclusion

Percutaneous splenic vein stent implantation for PPH treatment reduces the risk of gastrointestinal bleeding with minimal invasive. It has a high safety and reliable efficacy and is worthy of further clinical promotion.
Remnant cholesterol/high-density lipoprotein cholesterol ratio is a new powerful tool for identifying non-alcoholic fatty liver disease
Authors: Zou Yang , Hu Chong , Kuang Maobin , Chai Yuliang
Published: March 2022

Background

Remnant cholesterol/high-density lipoprotein cholesterol (RC/HDL-C) ratio has been shown to be a good predictor of metabolic disease risk, but no studies have further investigated the role of RC/HDL-C ratio in non-alcoholic fatty liver disease (NAFLD) patients.

Methods

The participants were 14,251 adults who underwent a physical examination, all of whom underwent abdominal ultrasonography to determine whether they had NAFLD. Receiver operating characteristic curve analysis and multivariate logistic regression models were used to assess the association between the RC/HDL-C ratio and the risk of NAFLD.

Results

Multivariate logistic regression analysis showed that after fully adjusting the confounding factors, the higher RC/HDL-C ratio was independently positively correlated with the risk of NAFLD. Interaction tests suggested that the effect of RC/HDL-C ratio on NAFLD was significantly affected by sex. Additionally, receiver operating characteristic curve analysis showed that the area under the curve of RC/HDL-C ratio for identifying NAFLD was 0.82, which was significantly higher than that of other conventional lipid parameters.

Conclusions

This study indicates for the first time that the higher RC/HDL-C ratio in the general population may be closely related to the increased risk of NAFLD.