bluuebunny/crossref_metadata_2025_split huggingface dataset:
TGFβ Signaling Activated by Cancer-Associated Fibroblasts Determines the Histological Signature of Lung Adenocarcinoma
Authors: Sato Ryo , Imamura Kosuke , Semba Takashi , Tomita Yusuke , Saeki Sho , Ikeda Koei , Komohara Yoshihiro , Suzuki Makoto , Sakagami Takuro , Saya Hideyuki , Arima Yoshimi 
Published: July 2021

AbstractInvasive lung adenocarcinoma (LADC) can be classified histologically as lepidic, acinar, papillary, micropapillary, or solid. Most LADC tumors manifest several of these histological subtypes, with heterogeneity being related to therapeutic resistance. We report here that in immunodeficient mice, human LADC cells form tumors with distinct histological features, MUC5AC-expressing solid-type or cytokeratin 7 (CK7)-expressing acinar-type tumors, depending on the site of development, and that a solid-to-acinar transition (SAT) could be induced by the tumor microenvironment. The TGFβ-Smad signaling pathway was activated in both tumor and stromal cells of acinar-type tumors. Immortalized cancer-associated fibroblasts (CAF) derived from acinar-type tumors induced SAT in 3D cocultures with LADC cells. Exogenous TGFβ1 or overexpression of an active form of TGFβ1 increased CK7 expression and reduced MUC5AC expression in LADC cells, and knockdown of Tgfb1 mRNA in CAFs attenuated SAT induction. RNA-sequencing analysis suggested that angiogenesis and neutrophil recruitment are associated with SAT in vivo. Our data indicate that CAF-mediated paracrine TGFβ signaling induces remodeling of tumor tissue and determines the histological pattern of LADC, thereby contributing to tumor heterogeneity.Significance:CAFs secrete TGFβ to induce a solid-to-acinar transition in lung cancer cells, demonstrating how the tumor microenvironment influences histological patterns and tumor heterogeneity in lung adenocarcinoma.
CD19/CD22 Dual-Targeted CAR T-cell Therapy for Relapsed/Refractory Aggressive B-cell Lymphoma: A Safety and Efficacy Study
Authors: Wei Guoqing , Zhang Yanlei , Zhao Houli , Wang Yiyun , Liu Yandan , Liang Bin , Wang Xiujian , Xu Huijun , Cui Jiazhen , Wu Wenjun , Zhao Kui , Nagler Arnon , Chang Alex H. , Hu Yongxian , Huang He 
Published: July 2021

Abstract

Chimeric antigen receptor (CAR) T-cell therapies that target either CD19 or CD22 alone have potent antilymphoma effects. However, antigen escape–mediated relapse often occurs. CAR T cells targeting both CD19 and CD22 may overcome this limitation. In this study, we developed bispecific CAR T cells simultaneously recognizing CD19- and CD22-expressing targets and assessed their safety and efficacy profiles in patients with relapsed/refractory aggressive B-cell lymphoma. Twenty-four patients were screened, and 16 were found eligible for the study. CAR T-cell–associated toxicities were recorded. Responses, overall survival (OS), and progression-free survival (PFS) were assessed. Of the 16 eligible patients, 14 (87.5%) achieved objective response and 10 (62.5%) achieved complete response (CR). The 2-year OS and PFS rates were 77.3% and 40.2%, respectively. Achieving CR (P = 0.046) and the number of prior chemotherapy lines (n = 2; P = 0.047) were independent prognostic factors associated with favorable PFS. The 2-year OS and PFS among patients who achieved CR were higher than among those who did not (P = 0.015 and P &lt; 0.001, respectively). The 2-year PFS among patients who received two prior lines of chemotherapy was higher than that among patients who received more than two lines of chemotherapy (P = 0.049); OS did not differ between the groups. Severe grade 4 cytokine-release syndrome (CRS) was observed in 1 patient; 4 and 11 patients had grades 1 and 2 CRS, respectively. No patients developed neurotoxicity. CD19/CD22 dual-targeted CAR T cells may be a safe, potent antilymphoma cell-based targeted immunotherapy.
US Database Study of Clinical Burden and Unmet Need in Recurrent Pericarditis
Authors: Klein Allan , Cremer Paul , Kontzias Apostolos , Furqan Muhammad , Tubman Ryan , Roy Mike , Lim‐Watson Michelle Z. , Magestro Matthew 
Published: July 2021

Background
Patients with recurrent pericarditis (RP) may develop complications, multiple recurrences, or inadequate treatment response. This study aimed to characterize disease burden and unmet needs in RP.

Methods and Results
This retrospective US database analysis included newly diagnosed patients with RP with ≥24 months of continuous history following their first pericarditis episode. RP was defined as ≥2 pericarditis episodes ≥28 days apart. Some patients had ≥2 recurrences, while others had a single recurrence with a serious complication, ie, constrictive pericarditis, cardiac tamponade, or a large pericardial effusion with pericardiocentesis/pericardial window. Among these patients with multiple recurrences and/or complications, some had features relating to treatment history, including long‐term corticosteroid use (corticosteroids started within 30 days of flare, continuing ≥90 consecutive days) or inadequate treatment response (pericarditis recurring despite corticosteroids and/or colchicine, or other drugs [excluding NSAIDs] within 30 days of flare, or prior pericardiectomy). Patients (N=2096) had hypertension (60%), cardiomegaly (9%), congestive heart failure (17%), atrial fibrillation (16%), autoimmune diseases (18%), diabetes mellitus (21%), renal disease (20%), anxiety (21%), and depression (14%). Complications included pericardial effusion (50%), cardiac tamponade (9%), and constrictive pericarditis (4%). Pharmacotherapy included colchicine (51%), NSAIDs (40%), and corticosteroids (30%), often in combination. This study estimates 37 000 US patients with RP; incidence was 6.0/100 000/year (95% CI, 5.6‒6.3), and prevalence was 11.2/100 000 (95% CI, 10.6‒11.7).

Conclusions
Patients with RP may have multiple recurrences and/or complications, often because of inadequate treatment response and persistent underlying disease. Corticosteroid use is frequent despite known side‐effect risks, potentially exacerbated by prevalent comorbidities. Substantial clinical burden and lack of effective treatments underscore the high unmet need.
Two Types of Four-Compartment Tefillin Cases from the Judean Desert Caves
Authors: Adler Yonatan 
Published: July 2021

Abstract
Approximately thirty tefillin cases were discovered in the Judean Desert. The publishers of these finds distinguished between single-compartment cases, which they identified as “arm-tefillin,” and four-compartment cases, which they identified as “head-tefillin.” Here I present a further typological distinction between two subtypes among the four-compartment tefillin cases: (1) the “simple-type,” in which a single line of stitching separates the compartments from one another, and (2) the “split-type,” in which the compartments are separated by incisions in the leather and each compartment is stitched closed individually. It seems likely that some kind of ritual issue is at stake, and an allusion to these two types as competing halakhic practices may be found in the tannaitic literature—with the rabbis ultimately rejecting the “split-type.” The Judean Desert finds may represent a synchronic debate between competing groups, a diachronic development, or perhaps practices followed contemporaneously by members of one and the same group.
The Critical Study of Religion and Division in the Age of Covid-19
Authors: Sexton Jason S. 
Published: July 2021

Abstract
The Covid-19 pandemic presented enormous challenges for secular and religious institutions as well as religion scholars engaged in the critical study of religion. The unique opportunities for scholars of religion include questions about the very nature of our academic work. Inclusive of scholarly research and dissemination, along with the administrative work and service that facilitates this, is academic work to draw from the rich wellspring of the traditions we study and represent, or does it neglect them in the daily affairs of our work? With a particular regional focus, and despite traditional academic disciplinary conventions within the critical study of religion, this article argues that religious traditions and the critical appropriations of their wisdom and ongoing actions provide an important reckoning with the reality of the ever-changing and often terrible conditions in the contemporary world. They provide a critical feature of what it means to cultivate an ecology of ethical responsibility and care.
The Problem of Dualistic Worldviews in a Season of Climate Change
Authors: Choi Sungho , Jung Ji Young 
Published: July 2021

Abstract
This article addresses the dualistic worldview surrounding climate change to be found among evangelicals in the United States. Since the majority of the traditionalist American evangelicals identify themselves with the Republican party, their views towards climate change tends to be highly skeptical: they tend to favour policies that protect the free-market economy. The Cornwall Alliance and its evangelical constituency, in particular, has provided a ground for a critical discussion concerning an association of Christian faith with conservative political ideologies from a particular biblical viewpoint. The key framework in the Alliance’s theological claims against environmentalism in general is an assumed dualism. This interpretive lens increases political bias/prejudice thereby impeding constructive discussion and a much needed co-operation between parties in the era of climate change.
Elder Sexual Abuse and Sexual Freedom in Faith-based Residential Care Facilities: Ethical Dilemmas, and Institutional Integrity
Authors: Miller Virginia , Miller Seumas , Stevens Bruce 
Published: July 2021

Abstract
The issues of elder sexual abuse and sexual freedom in residential care facilities are complicated by the existence of many residents with cognitive impairments of a kind that compromise their ability to make decisions based on informed consent. The issues of elder sexual abuse and sexual freedom in faith-based residential care facilities, in particular, are further complicated by restrictive, theologically based, ethical principles pertaining to sexual activity – for instance, prohibitions on extra-marital sex and the use of prostitutes by residents. The tension that arises must necessarily deal with the integrity of faith-based aged-care facilities and current legislation that promotes the rights of age-care residents to sexual freedoms. In the midst of much public concern about the level and quality of institutional age care this particular aspect seldom attracts notice. It nevertheless exposes a quandary to do with how ought public theology and ethics respond.
New Evidence on the Saruhanid Dynasty
Authors: Zachariadou † Elizabeth A. , Dendrinos Charalambos 
Published: July 2021

Abstract
The article offers new evidence on the Saruhanid succession in the fourteenth century in light of a short chronicle contained in a Greek manuscript housed in the Bodleian Library, Oxford, which records a hitherto unknown internal conflict that took place in 1383. This and similar historical evidence reflect the continuity of life of the Greek Orthodox communities under the Turcoman conquerors in a period marked by the increasing decline of Byzantine power and the rise of the Ottomans.
Use of N-Acetylcysteine for Clozapine-Induced Acute Liver Injury: A Case Report and Literature Review
Authors: Shah Jenny , Muir Justin , Furfaro David , Beitler Jeremy R. , Dzierba Amy L. 
Published: July 2021

Purpose: To report a case of clozapine-induced hepatotoxicity managed with intravenous (IV) N-acetylcysteine (NAC) and summarize the available literature. Summary: A 46-year-old woman with history of bipolar disorder with psychotic features presented to the intensive care unit with asterixis and elevations in liver enzymes. The patient had been initiated on risperidone, clozapine, and lithium approximately 1 month prior to admission. After ruling out other possible non-drug etiologies, clozapine was suspected as the likeliest cause of the acute liver injury. Her acute liver injury was managed with the discontinuation of all antipsychotics, administration of IV NAC, and other standard of care supportive measures. Conclusion: Although clozapine has been associated with hepatitis and acute liver failure, there are no reports of NAC used in the management of clozapine-induced hepatotoxicity. NAC was used in our patient after considering the potential benefit and limited adverse effects. The role of NAC in non–acetaminophen-induced acute liver failure remains promising, but more research is warranted.
Thermomechanical properties of silica–epoxy nanocomposite modified by hyperbranched polyester: A molecular dynamics simulation
Authors: Zhang Jianwen , Wang Dongwei , Wang Lujia , Zuo Wanwan , Ma Xiaohua , Du Shuai , Zhou Lijun 
Published: July 2021

In this article, pure epoxy resin and silica–epoxy nanocomposite models were established to investigate the effects of hyperbranched polyester on microstructure and thermomechanical properties of epoxy resin through molecular dynamics simulation. Results revealed that the composite of silica can improve the thermomechanical properties of nanocomposites, including the glass transition temperature, thermal conductivity, and elastic modulus. Moreover, the thermomechanical properties were further enhanced through chemical modification on the silica surface, where the effectiveness was the best through grafting hyperbranched polyester on the silica surface. Compared with pure epoxy resin, the glass transition temperature of silica–epoxy composite modified by silica grafted with hyperbranched polyester increased by 38 K. The thermal conductivity increased with the increase of temperature and thermal conductivity at room temperature increased to 0.4171 W/(m·K)−1 with an increase ratio of 94.3%. Young’s modulus, volume modulus, and shear modulus all fluctuated as temperature rise with a down overall trend. They increased by 44.68%, 29.52%, and 36.65%, respectively, when compared with pure epoxy resin. At the same time, the thermomechanical properties were closely related to the microstructure such as fractional free volume (FFV), mean square displacement (MSD), and binding energy. Silica surface modification by grafting hyperbranched polyester reduced the FFV value and MSD value most and strengthened the combination of silica and epoxy resin matrix the best, resulting in the best thermomechanical properties.
Calcaneal Reconstruction With Free Deep Circumflex Iliac Artery Osseocutaneous Flap Following Aggressive Benign Bone Tumor Resection
Authors: Rosli Mohamad Aizat , Wan Ismail Wan Faisham , Wan Sulaiman Wan Azman , Mat Zin Nor Azman , Abdul Halim Syurahbil , Mat Johar Fatimah , Mat Saad Arman Zaharil , Halim Ahmad Sukari 
Published: July 2021

Background: Advances in limb-salvage techniques have made total calcanectomy and primary reconstruction possible in managing calcaneal aggressive benign tumors and selected cases of intraosseous malignant tumors. However, there is still no consensus on the operative approach, oncologic margin, and the best reconstruction method to date. These 2 cases describe our experience in calcaneal reconstruction with the free deep circumflex iliac artery (DCIA) osseocutaneous flap in benign aggressive calcaneal tumors. Methods: We reported 2 consecutive male and female patients, with an average age of 25 years (age 19 and 31, respectively), who underwent total calcanectomy and primary calcaneal reconstruction with the free DCIA osseocutaneous flaps for calcaneal chondroblastoma and giant cell tumor. A marginal resection of the entire calcaneus through the subtalar and calcaneocuboid joints (intra-articular approach) was performed in the first case and a wide local resection leaving 1 cm normal calcaneal bone margin anterosuperiorly (intraosseous approach) was performed in the second case. Results: The follow-up period averaged 48 months. Negative oncologic margins were achieved in both cases. The first case was complicated with venous thrombosis; however, the graft remained viable after emergency reexploration. Normal foot function was restored with good solid osseous union and bony hypertrophy observed. Both patients achieved good short-term functional and aesthetic outcomes with no donor site pain or disability. No local recurrence was reported either. Conclusion: Primary calcaneal reconstruction with the free DCIA osseocutaneous flap can lead to good short-term functional and aesthetic outcomes. Level of Evidence: Level IV, case series.
Traditional Practitioners and Nurses’ Perspectives on Traditional Medicine Utilisation During Antenatal Care in Matabeleland South Province, Zimbabwe
Authors: Mudonhi Nicholas , Nunu Wilfred Njabulo 
Published: July 2021

Background: Traditional Health System has been reported to be the most accessible, affordable, and acceptable in resource-poor settings, particularly in Sub-Saharan Africa. It is utilised for different health needs, including pregnancy management. This study sought to explore traditional and Nurses’ perspectives on traditional medicine utilisation during antenatal care in Bulilima District, Plumtree, Zimbabwe. Methods: A qualitative survey was conducted on purposively selected nurses’ and snowballed traditional health practitioners who responded to unstructured interviews. Data were collected using a digital tape recorder, transcribed, and thematically analysed on Max Qualitative Data Analysis. Results: A total of 6 superordinate and 10 subordinate themes emerged from the collected and analysed data on both traditional practitioners and nurses. The superordinate themes associated with Traditional Medicine utilisation during pregnancy by women were: protective role, beliefs, shortening of labour, cleansing, accessibility, and collaboration between traditional practitioners and modern health practitioners. Nurses expressed their skepticism on the safety and efficacy of traditional medicine utilisation during pregnancy. Conclusion: Women utilise traditional medicines and remedies during pregnancy for different reasons, such as protection from evil spirits, foetus growth and shortening labour. There are concerns regarding their safety from the health service providers, although traditional practitioners share a different view. There is a need for investing in research that would ascertain the safety of these traditional medicines as this system has been a cheaper alternative for those who cannot afford or access modern health services.
Atmospheric circulation and mortality by unintentional drowning in Spain: from 1999 to 2018
Authors: Real Á del , Sanchez-Lorenzo A , Lopez-Bustins J-A , Zarrabeitia MT , Santurtún A 
Published: July 2021

Aims: Drowning deaths are a leading cause of unintentional deaths worldwide. Few studies have analysed the role of meteorology in drowning, and with inconclusive results. The aim of this work is to analyse the temporal and geographical distribution of deaths by accidental drowning and submersion in Spain over 20 years, and to assess the relationship between accidental drowning and main atmospheric circulation patterns. Methods: An ecological study was performed, in which drowning and submersion mortality data from 1999 to 2018, considering demographic variables, were analysed. To study the association with atmospheric circulation we used an ERA5 reanalysis product over the whole European continent and the Climatic Research Unit Time Series (CRU TS) data set. Results: The annual average rate of deaths by accidental drownings was 11.86 deaths per million of habitants in Spain. The incidence in males was four times higher than in females, and when comparing age groups, the rate in the eldest group was the highest. Unintentional drowning deaths were not equally distributed around the country; the provinces with the highest registered standardized drowning death rates were touristic waterfront provinces either in Eastern Spain or in one of the archipelagos. There was a significant relationship between accidental drowning and meteorological variables during summer months, and drowning deaths were spatially correlated with sea-level pressure over the Mediterranean basin. Conclusion: Although the mortality rate registered a statistically significant decreasing tendency over the studied period, our results must be taken into consideration to improve the prevention strategies in the country since most of these deaths are avoidable.
Etiology of Cartilage Lesions Does Not Affect Clinical Outcomes of Patellofemoral Autologous Chondrocyte Implantation
Authors: Mestriner Alexandre Barbieri , Ackermann Jakob , Merkely Gergo , Galvão Pedro Henrique Schmidt Alves Ferreira , Ambra Luiz Felipe Morlin , Gomoll Andreas H. 
Published: July 2021

Objective To determine the relationship between cartilage lesion etiology and clinical outcomes after second-generation autologous chondrocyte implantation (ACI) in the patellofemoral joint (PFJ) with a minimum of 2 years’ follow-up. Methods A retrospective review of all patients that underwent ACI in the PFJ by a single surgeon was performed. Seventy-two patients with a mean follow-up of 4.2 ± 2.0 years were enrolled in this study and were stratified into 3 groups based on the etiology of PFJ cartilage lesions: patellar dislocation (group 1; n = 23); nontraumatic lesions, including chondromalacia, osteochondritis dissecans, and degenerative defects (group 2; n = 28); and other posttraumatic lesions besides patellar dislocations (group 3; n = 21). Patient’s mean age was 29.6 ± 8.7 years. Patients in group 1 were significantly younger (25.4 ± 7.9 years) than group 2 (31.7 ± 9.6 years; P = 0.025) and group 3 (31.5 ± 6.6 years; P = 0.05). Body mass index averaged 26.2 ± 4.3 kg/m2, with a significant difference between group 1 (24.4 ± 3.2 kg/m2) and group 3 (28.7 ± 4.5 kg/m2; P = 0.005). A clinical comparison was established between groups based on patient-reported outcome measures (PROMs) and failure rates. Results Neither pre- nor postoperative PROMs differed between groups ( P > 0.05). No difference was seen in survivorship between groups (95.7% vs. 82.2% vs. 90.5%, P > 0.05). Conclusion Cartilage lesion etiology did not influence clinical outcome in this retrospective study after second generation ACI in the PFJ. Level of Evidence Level III, retrospective comparative study.