bluuebunny/crossref_metadata_2025 huggingface dataset:
Aggressive B-cell Lymphoma with MYC/TP53 Dual Alterations Displays Distinct Clinicopathobiological Features and Response to Novel Targeted Agents
Authors: Deng Manman , Xu-Monette Zijun Y. , Pham Lan V. , Wang Xudong , Tzankov Alexandar , Fang Xiaosheng , Zhu Feng , Visco Carlo , Bhagat Govind , Dybkaer Karen , Chiu April , Tam Wayne , Zu Youli , Hsi Eric D. , You Hua , Huh Jooryung , Ponzoni Maurilio , Ferreri Andrés J.M. , Møller Michael B. , Parsons Benjamin M. , Hagemeister Fredrick , van Krieken J. Han , Piris Miguel A. , Winter Jane N. , Li Yong , Xu Bing , Liu Phillip , Young Ken H.
Published: November 2020

Diffuse large B-cell lymphoma (DLBCL) is the major type of aggressive B-cell lymphoma. High-grade B-cell lymphoma (HGBCL) with MYC/BCL2 double-hit (DH) represents a distinct entity with dismal prognosis after standard immunochemotherapy in the current WHO lymphoma classification. However, whether TP53 mutation synergizes with MYC abnormalities (MYC rearrangement and/or Myc protein overexpression) contributing to HGBCL-like biology and prognosis is not well investigated. In this study, patients with DLBCL with MYC/TP53 abnormalities demonstrated poor clinical outcome, high-grade morphology, and distinct gene expression signatures. To identify more effective therapies for this distinctive DLBCL subset, novel MYC/TP53/BCL-2–targeted agents were investigated in DLBCL cells with MYC/TP53 dual alterations or HGBCL-MYC/BCL2-DH. A BET inhibitor INCB057643 effectively inhibited cell viability and induced apoptosis in DLBCL/HGBCL cells regardless of MYC/BCL2/TP53 status. Combining INCB057643 with a MDM2-p53 inhibitor DS3032b significantly enhanced the cytotoxic effects in HGBCL-DH without TP53 mutation, while combining with the BCL-2 inhibitor venetoclax displayed potent therapeutic synergy in DLBCL/HGBCL cells with and without concurrent TP53 mutation. Reverse-phase protein arrays revealed the synergistic molecular actions by INCB057643, DS3032b and venetoclax to induce cell-cycle arrest and apoptosis and to inhibit AKT/MEK/ERK/mTOR pathways, as well as potential drug resistance mechanisms mediated by upregulation of Mcl-1 and RAS/RAF/MEK/ERK pathways. In summary, these findings support subclassification of DLBCL/HGBCL with dual MYC/TP53 alterations, which demonstrates distinct pathobiologic features and dismal survival with standard therapy, therefore requiring additional targeted therapies.

Implications:

The clinical and pharmacologic studies suggest recognizing DLBCL with concomitant TP53 mutation and MYC abnormalities as a distinctive entity necessary for precision oncology practice.

Visual Overview:

http://mcr.aacrjournals.org/content/molcanres/19/2/249/F1.large.jpg.
Serum Lysyl Oxidase Is a Potential Diagnostic Biomarker for Kidney Fibrosis
Authors: Zhang Xiao-qin , Li Xin , Zhou Wen-qian , Liu Xi , Huang Jie-li , Zhang Ying-ying , Lindholm Bengt , Yu Chen
Published: November 2020

Background: Kidney fibrosis is the ultimate consequence of advanced stages of chronic kidney disease (CKD); however, there are currently no reliable biomarkers or noninvasive diagnostic tests available for the detection of kidney fibrosis. Lysyl oxidase (LOX) promotes collagen cross-linking, and serum LOX levels have been shown to be elevated in patients with fibrosis of the heart, lungs, and liver. However, serum LOX levels have not been reported in patients with kidney fibrosis. We explored whether serum LOX levels are associated with kidney fibrosis. Method: Overall, 202 patients with kidney disease underwent renal biopsy, scoring of kidney fibrosis, and determination of the area of kidney fibrosis. LOX levels were measured in serum and in kidney tissues. We analyzed the association of circulating LOX and tissue LOX levels with the scores and areas of kidney fibrosis. LOX expression was also investigated with in vitro and in vivo kidney fibrosis models. Results: Serum LOX levels were higher in patients with kidney fibrosis than in those without kidney fibrosis (p < 0.001) and higher in patients with moderate-severe kidney fibrosis than in patients with mild kidney fibrosis (p < 0.001). Both serum LOX and renal tissue LOX levels correlated with the area of kidney fibrosis (r = 0.748, p < 0.001; r = 0.899, p < 0.001, respectively). Receiver operating characteristic curve analysis of serum LOX levels showed an area under the curve of 0.80 (95% CI: 0.74–0.86). The optimal serum LOX level cutoff point was 253.34 pg/mL for the prediction of kidney fibrosis and 306.56 pg/mL for the prediction of moderate-severe kidney fibrosis. LOX expression levels were significantly upregulated (2.3–2.6 and 6-fold, respectively) in in vitro and in vivo interstitial fibrosis models. Conclusions: Both serum LOX and tissue LOX levels correlated with the presence and degree of kidney fibrosis in patients with CKD. These results suggest that serum LOX levels could potentially serve as a noninvasive diagnostic biomarker for kidney fibrosis and may further potentially serve as a stratified biomarker for the identification of mild and moderate-severe kidney fibrosis.
Cytomorphologic Features of Gastric-Type Endocervical Adenocarcinoma in Liquid-Based Preparations
Authors: Schwock Joerg , Starova Blerta , Khan Zanobia F. , Mirkovic Jelena , Parra-Herran Carlos , Ko Hyang Mi , Rouzbahman Marjan , Ghorab Zeina
Published: November 2020

Objective: Gastric-type endocervical adenocarcinoma (GAS) is a recently described, uncommon, and aggressive tumor with distinct morphologic features and HPV-independent etiology. Data on GAS in liquid-based cytology (LBC) Papanicolaou (Pap) test preparations from a North American patient population are scant. We systematically assessed the cytomorphologic characteristics of GAS in LBC from patients in Ontario and examined if glandular cell nuclear area could represent a readily assessable feature which may aid in GAS detection. Study Design: Pap test slides preceding the diagnosis of GAS were retrieved locally or requested from outside laboratories. A structured review of 15 cytomorphologic features was performed using the available LBC Pap test slides of GAS and a set of usual-type endocervical adenocarcinomas (UEA). Morphometry of the glandular cell nuclear area was performed, and normalized values were compared to UEA and benign endocervical cells. Results: At least 1 Pap test (5 ThinPrep®, 11 SurePath®, and 1 direct smear) was available for 14 patients. Original LBC Pap test diagnoses were negative for intraepithelial lesion or malignancy (NILM) (7), adenocarcinoma/carcinoma (6), atypical glandular cells (2), and adenocarcinoma in situ (1). Review detected abnormal glandular cells in 6/7 NILM cases. Honeycomb-like sheets, nuclear enlargement, and microvesicular cytoplasm were the single most common architectural, nuclear, and cytoplasmic features, respectively. Microvesicular cytoplasm (100 vs. 17%), honeycomb-like sheets (87 vs. 8%), prominent nucleoli (93 vs. 25%), and anisonucleosis (93 vs. 50%) were most discriminatory for GAS versus UEA, respectively. Yellow mucin, intranuclear cytoplasmic pseudoinclusions, and goblet/Paneth-like cells were uncommon, but unique for GAS. Glandular cell nuclear area normalized to neutrophils was found to be significantly increased in GAS compared to benign endocervical cells. Conclusions: GAS is under-recognized and may mimic reactive endocervical cells. Awareness of the tumor type and its cytomorphology is critical for early detection. Identification of glandular cells with uniform nuclear enlargement in conjunction with any of the other cytologic features may help avoid false-negative Pap results. Neutrophils may serve as convenient size reference and visual aid.
Subacute Thyroiditis from COVID-19 Infection: A Case Report and Review of Literature
Authors: Khatri Akshay , Charlap Esti , Kim Angela
Published: November 2020

Introduction: The novel severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) virus has led to the ongoing Coronavirus disease 2019 (COVID-19) disease pandemic. There are increasing reports of extrapulmonary clinical features of COVID-19, either as initial presentations or sequelae of disease. We report a patient diagnosed with subacute thyroiditis precipitated by COVID-19 infection, as well as review the literature of similar cases. Case Presentation: A 41-year-old female with no significant personal or family history of endocrinologic disorders presented with clinical features of thyroiditis that began after COVID-19 infection. Clinical, laboratory, and radiologic findings were indicative of subacute thyroiditis. Workup for potential triggers other than SARS-CoV-2 was negative. Discussion/Conclusion: We compared the clinical and diagnostic findings of our patient with other well-documented cases of subacute thyroiditis presumed to be triggered by SARS-CoV-2 viral infection. We also reviewed the literature related to the potential mechanisms leading to thyroiditis. Clinicians must be aware of the possibility of thyroid dysfunction after COVID-19 infection. Early recognition and timely anti-inflammatory therapy help in successful management.
Inquérito populacional sobre a funcionalidade das pessoas com lesão medular no Brasil
Authors: Utiyama Daniela Mitiyo Odagiri , Alfieri Fabio Marcon , Battistella Linamara Rizzo
Published: November 2020

A pesquisa InSCI (International spinal cord injury) foi desenvolvida para descrever a saúde e o bem-estar de indivíduos com lesão medular (LM) em relação à comunidade local. Por isto, objetivo deste estudo será descrever as características pessoais, fatores ambientais, de saúde, de qualidade de vida, de trabalho dos indivíduos que vivem com lesão medular no Brasil e comparar os dados com outros países participantes da pesquisa. Este estudo deverá ser de caráter transversal observacional. Os indivíduos com LM serão recrutados no Instituto de Medicina Física e de Reabilitação (IMREA) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, na Rede de Reabilitação Lucy Montoro (IRLM) e na Associação Fluminense de Reabilitação (AFR). Participarão do estudo 400 indivíduos de ambos os sexos com idade igual ou superior a 18 anos com diagnóstico de lesão medular de origem traumática cujo tempo de lesão esteja superior a 3 meses. Os voluntários realizarão uma avaliação inicial por meio de questionário com 125 perguntas sobre problemas de saúde, atividade e participação, independência nas atividades de vida diária, trabalho, fatores ambientais e pessoais, serviços de saúde e qualidade de vida. As associações entre as variáveis serão feitas testes de correlação de Pearson ou Spearman. Modelos simples de regressão linear ou logística também poderão ser usados de acordo com os dados obtidos. Os procedimentos de processamento e ajuste de dados obedecerão às recomendações das Diretrizes Cross-Cultural Survey (CCSG) e ao fortalecimento do Relatório de Estudos Observatórios em Epidemiologia (STROBE).
Atividade física como fator protetor para o extremo baixo peso em idosos assistidos por uma operadora de saúde
Authors: Silva Deborah Lorenzo Gomez , D'Oliveira Rafaela Ramos , Kim Beatriz Myung Jin , Santos Ana Flávia de Lima , Silva Junior Eduardo Antonio Barros , Oliveira Henrique Souza Barros de , Manso Maria Elisa Gonzalez
Published: November 2020

Objetivo: Investigar a influência de fatores relacionados aos aspectos multidimensionais do envelhecimento em um grupo de idosos com baixo peso assistidos pelo setor privado de saúde. Métodos: Estudo transversal conduzido com 243 idosos com índice de massa corpórea <23 kg/m², todos assistidos por uma operadora de planos de saúde, no município de São Paulo, SP, Brasil, alocados em dois grupos: baixo peso e extremo baixo peso. Para a coleta dos dados empregou-se inquérito contendo informações relacionadas aos aspectos multidimensionais do envelhecimento. Os dados obtidos foram submetidos a análise descritiva das variáveis, com posterior análise comparativa através dos testes t Student e Qui-Quadrado ou exato de Fisher, quando necessário. Para variáveis com significância estatística, aplicou-se regressão logística e calculou-se as Odds Ratio, com intervalo de confiança de 95%. Resultados: Observou-se que, a idade avançada (p=0,044), dificuldade de mobilidade (p=0,011) e baixos níveis de atividade física (p=0.021) influenciam significativamente os idosos em estado nutricional de extremo baixo peso. Por meio do modelo de regressão logística, verificou-se que para cada uma hora de atividade física praticada pelos idosos deste grupo, os riscos de evolução para extremo baixo peso diminuem em até 14%. Conclusão: A pratica regular e orientada de atividade física praticada por idosos com algum grau de déficit nutricional é capaz de prevenir e/ou retardar desfechos indesejados em grupos susceptíveis.
Altered Macrophage Polarization Induces Experimental Pulmonary Hypertension and Is Observed in Patients With Pulmonary Arterial Hypertension
Authors: Zawia Amira , Arnold Nadine D. , West Laura , Pickworth Josephine A. , Turton Helena , Iremonger James , Braithwaite Adam T. , Cañedo Jaime , Johnston Simon A. , Thompson A.A. Roger , Miller Gaynor , Lawrie Allan
Published: November 2020

Objective:

To determine whether global reduction of CD68 (cluster of differentiation) macrophages impacts the development of experimental pulmonary arterial hypertension (PAH) and whether this reduction affects the balance of pro- and anti-inflammatory macrophages within the lung. Additionally, to determine whether there is evidence of an altered macrophage polarization in patients with PAH.

Approach and Results:

Macrophage reduction was induced in mice via doxycycline-induced CD68-driven cytotoxic diphtheria toxin A chain expression (macrophage low [MacLow] mice). Chimeric mice were generated using bone marrow transplant. Mice were phenotyped for PAH by echocardiography and closed chest cardiac catheterization. Murine macrophage phenotyping was performed on lungs, bone marrow–derived macrophages, and alveolar macrophages using immunohistochemical and flow cytometry. Monocyte-derived macrophages were isolated from PAH patients and healthy volunteers and polarization capacity assessed morphologically and by flow cytometry. After 6 weeks of macrophage depletion, male but not female MacLow mice developed PAH. Chimeric mice demonstrated a requirement for both MacLow bone marrow and MacLow recipient mice to cause PAH. Immunohistochemical analysis of lung sections demonstrated imbalance in M1/M2 ratio in male MacLow mice only, suggesting that this imbalance may drive the PAH phenotype. M1/M2 imbalance was also seen in male MacLow bone marrow–derived macrophages and PAH patient monocyte-derived macrophages following stimulation with doxycycline and IL (interleukin)-4, respectively. Furthermore, MacLow-derived alveolar macrophages showed characteristic differences in terms of their polarization and expression of diphtheria toxin A chain following stimulation with doxycycline.

Conclusions:

These data further highlight a sex imbalance in PAH and further implicate immune cells into this paradigm. Targeting imbalance of macrophage population may offer a future therapeutic option.
Cardiovascular- and Bleeding-Related Hospitalization Rates With Edoxaban Versus Warfarin in Patients With Atrial Fibrillation Based on Results of the ENGAGE AF–TIMI 48 Trial
Authors: Vilain Katherine , Li Haiyan , Kwong Wingham J. , Antman Elliott M. , Ruff Christian T. , Braunwald Eugene , Cohen David J. , Giugliano Robert P. , Magnuson Elizabeth A. ,   on behalf of the ENGAGE AF-TIMI 48 Trial Investigators
Published: November 2020

Background

The ENGAGE AF–TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48) demonstrated noninferiority of once-daily 60 mg (30 mg dose-reduced) edoxaban compared with warfarin for prevention of stroke/systemic embolism in patients with atrial fibrillation. No previous analysis has explored the impact of treatment with edoxaban versus warfarin on rates of hospitalizations.

Methods

Detailed healthcare resource utilization data from ENGAGE AF–TIMI 48 for the 14 024 randomized patients who received at least one dose of study drug were used to compare the rates of bleeding- and cardiovascular-related hospitalizations for edoxaban versus warfarin. Hospitalization rates were calculated for each treatment group, and relative rates were estimated using Poisson regression. The influence of patient characteristics on the impact of edoxaban versus warfarin was evaluated through the inclusion of interaction terms.

Results

The overall rate of cardiovascular- or bleeding-related hospitalization was significantly lower for edoxaban than warfarin (relative rate [RR], 0.91 [95% CI, 0.85–0.97],
P
=0.003). Rates of hospitalizations for cardiovascular reasons (RR, 0.91 [95% CI, 0.85–0.97],
P
=0.004), stroke (RR, 0.80 [95% CI, 0.72–0.88],
P
<0.0001), and for each stroke subtype (ischemic: RR, 0.89 [95% CI, 0.81–0.99],
P
=0.03; hemorrhagic: RR, 0.60 [95% CI, 0.54–0.68],
P
<0.0001) were also lower for edoxaban. Notably, significantly greater reductions with edoxaban versus warfarin were seen for ischemic stroke–related hospitalizations in vitamin K antagonist naive patients and patients with CHADS
2
scores 4 to 6, previous stroke or transient ischemic attack, age ≥75, and no previous coronary artery disease. For nonstroke bleeding–related hospitalizations, greater reductions with edoxaban were seen in vitamin K antagonist naive patients, patients with CHADS
2
scores 4 to 6, and patients with moderate renal dysfunction.

Conclusions

Edoxaban 60 mg (30 mg dose-reduced) was associated with a significantly lower overall rate of cardiovascular- or bleeding-related hospitalization and significant reductions in the subcategories of cardiovascular-related, stroke-related, bleed-related, and nonstroke cardiovascular–related hospitalizations, when compared with warfarin. These results suggest the potential for cost offsets with edoxaban, with even greater reductions in higher-risk patients.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT00781391
Reduction in Revascularization With Icosapent Ethyl
Authors: Peterson Benjamin E. , Bhatt Deepak L. , Steg Ph. Gabriel , Miller Michael , Brinton Eliot A. , Jacobson Terry A. , Ketchum Steven B. , Juliano Rebecca A. , Jiao Lixia , Doyle Ralph T. , Granowitz Craig , Gibson C. Michael , Pinto Duane , Giugliano Robert P. , Budoff Matthew J. , Tardif Jean-Claude , Verma Subodh , Ballantyne Christie M. ,   On behalf of the REDUCE-IT Investigators
Published: November 2020

Background:

Patients with elevated triglycerides despite statin therapy have increased risk for ischemic events, including coronary revascularizations.

Methods:

REDUCE-IT (The Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial), a multicenter, double-blind, placebo-controlled trial, randomly assigned statin-treated patients with elevated triglycerides (135–499 mg/dL), controlled low-density lipoprotein (41–100 mg/dL), and either established cardiovascular disease or diabetes plus other risk factors to receive icosapent ethyl 4 g/d or placebo. The primary and key secondary composite end points were significantly reduced. Prespecified analyses examined all coronary revascularizations, recurrent revascularizations, and revascularization subtypes.

Results:

A total of 8179 randomly assigned patients were followed for 4.9 years (median). First revascularizations were reduced to 9.2% (22.5/1000 patient-years) with icosapent ethyl versus 13.3% (33.7/1000 patient-years) with placebo (hazard ratio, 0.66 [95% CI, 0.58–0.76];
P
<0.0001; number needed to treat for 4.9 years=24); similar reductions were observed in total (first and subsequent) revascularizations (negative binomial rate ratio, 0.64 [95% CI, 0.56–0.74];
P
<0.0001), and across elective, urgent, and emergent revascularizations. Icosapent ethyl significantly reduced percutaneous coronary intervention (hazard ratio, 0.68 [95% CI, 0.59–0.79];
P
<0.0001) and coronary artery bypass grafting (hazard ratio, 0.61 [95% CI, 0.45–0.81];
P
=0.0005).

Conclusions:

Icosapent ethyl reduced the need for first and subsequent coronary revascularizations in statin-treated patients with elevated triglycerides and increased cardiovascular risk. To our knowledge, icosapent ethyl is the first non–low-density lipoprotein–lowering treatment that has been shown to reduce coronary artery bypass grafting in a blinded, randomized trial.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01492361.
Oral Carriage of
Streptococcus mutans
Harboring the
cnm
Gene Relates to an Increased Incidence of Cerebral Microbleeds
Authors: Hosoki Satoshi , Saito Satoshi , Tonomura Shuichi , Ishiyama Hiroyuki , Yoshimoto Takeshi , Ikeda Shuhei , Ikenouchi Hajime , Yamamoto Yumi , Hattori Yorito , Miwa Kaori , Friedland Robert P. , Carare Roxana O. , Nakahara Jin , Suzuki Norihiro , Koga Masatoshi , Toyoda Kazunori , Nomura Ryota , Nakano Kazuhiko , Takegami Misa , Ihara Masafumi
Published: November 2020

Background and Purpose:

Cerebral microbleeds (CMB) are associated with stroke and cognitive impairment. We previously reported a high prevalence of CMB in people with
Streptococcus mutans
expressing Cnm, a collagen-binding protein in the oral cavity.
S.
mutans
is a major pathogen responsible for dental caries. Repeated challenge with
S.
mutans
harboring the
cnm
gene encoding Cnm induced cerebral bleeding in stroke-prone spontaneously hypertensive rats. The purpose of this longitudinal study is to examine the relationship of
cnm
-positive
S.
mutans
to the development of CMB.

Methods:

We retrospectively investigated patients with stroke receiving oral microbiological examination and head 3T magnetic resonance imaging evaluations twice in the period 2014 to 2019, allowing >180-day interval. Patients with
cnm
-positive
S.
mutans
were compared with those without. Quasi-Poisson regression models were used to explore associations between
cnm
-positive
S.
mutans
and the increase in number of CMB between the 2 magnetic resonance imaging scans.

Results:

A total of 111 patients were identified; 21 (19%) with
cnm
-positive
S.
mutans
and 90 (81%) without. Clinical history, including blood pressure and the use of antithrombotic agents, were comparable between the 2 groups. New CMB were more commonly observed in patients with
cnm
-positive
S.
mutans
(52% versus 23%;
P
=0.008). The incidence of CMB was significantly higher in the group with
cnm
-positive
S.
mutans
, especially in deep areas, (incidence rate ratios [95% CI], 5.1 [1.9–13.6] for CMB in any brain region; 15.0 [5.4–42.0] for deep CMB), which persisted after adjusting for age, sex, hypertension, and renal impairment (4.7 [1.8–11.9] for CMB in any brain region; 13.9 [4.3–44.5] for deep CMB).

Conclusions:

This study demonstrates that
cnm
-positive
S.
mutans
is associated with an increased incidence of CMB. Treatment for
cnm
-positive
S.
mutans
infection may be a novel microbiota-based therapeutic approach for stroke and cognitive impairment.
Drinking Patterns and Risk of Ischemic Stroke in Middle-Aged Adults
Authors: Yang Wookjin , Kang Dong-Wan , Ha Sue Young , Lee Seung-Hoon
Published: November 2020

Background and Purpose:

Although it has been reported that the amount of alcohol consumption has a J-shaped association with ischemic stroke, it is unclear whether differences in drinking patterns affect this relationship. We aimed to clarify the impact of drinking patterns on ischemic stroke in midlife.

Methods:

We used data from the National Health Insurance Service-National Sample Cohort, which is a large-sized, standardized population cohort in Korea. Five different drinking patterns were defined by combining the frequency of alcohol consumption and quantity of alcohol consumed per occasion, that is, abstainers, not drinking alcohol; drinker group I, ≤30 g/d and <5 d/wk; drinker group II, ≤30 g/d and ≥5 d/wk; drinker group III, >30 g/d and <5 d/wk; and drinker group IV, >30 g/d and ≥5 d/wk. The association between the drinking patterns and ischemic stroke occurrence was analyzed using the Cox proportional hazard model.

Results:

A total of 152 469 middle-aged participants (mean age, 50.2 years; 72 285 men [47.4%]) were eligible for the analyses. The median follow-up time was 9.0 years. Compared with abstainers, those who drank <5 d/wk (drinker groups I and III) had a significantly lower risk of ischemic stroke (group I hazard ratio, 0.71 [95% CI, 0.59–0.85]; group III hazard ratio, 0.80 [95% CI, 0.68–0.93]) during the first 7 years from the baseline, while other drinker groups showed no such differences. However, the effect of drinking patterns on ischemic stroke risk was attenuated after the first 7 years.

Conclusions:

Reduced risk of ischemic stroke was observed in middle-aged participants with specific drinking patterns, but it was limited to the earlier period. Physicians should be cautious in educating patients on alcohol consumption, considering the long-term association between drinking patterns and ischemic stroke.
Introduction
Authors: Dahlgren Susanne , Lindbekk Monika
Published: November 2020

This article focuses on adjudication of Muslim family law in countries that range from the Middle East and North Africa to South-East Asia. It begins by shortly summarizing the development of shari‘a in pre-modern times, up until the 19th century. We discuss the basic features of marriage among classical jurists and argue that the close connection known today between the family and Islamic law can be traced to the emergence of modern nation states and centralizing state structures. We then provide a description of important personal status reforms during the 20th and 21st centuries and consider the growing body of scholarship that engages with adjudication of Muslim family law in action and in context. Finally, we consider the contribution that the articles contained in the special double issue make to the field of research, including the questions of gender and judicial authority, religion-based judicial activism, and the courts’ involvement in larger socio-political processes.
“I’ll Dance for You, I’ll Dance for Me, I’ll Dance for the Sake of Dancingˮ
Authors: Gottesfeld Dorit
Published: November 2020

This article examines ʿAtaba thaqīlat al-rūḥ (“Threshold of heavy spirit,” 2011), a novel by the new generation West Bank writer Māyā Abū l-Ḥayāt, who is considered one of the prominent new generation Palestinian West Bank writers, in which diverse and unique use of a dance motif is found. The article reviews the history of dance in Arab society and the meanings that it had in the past and currently has in Arab society and culture. It illustrates how Abū l-Ḥayāt uses each of these meanings throughout her novel in order to reveal the female soul and the status of women in Arab society. The article shows how Abū l-Ḥayāt incorporates this motif into her novel in a unique and original way, thus exposing woman’s yearning for freedom, creating a new feminine language and undermining accepted norms.
Cross Scripts: Inscribing Hebrew into Jewish American Literature
Authors: Wirth-Nesher Hana
Published: November 2020

Most Jewish immigrants to America during the early 20th century arrived speaking Yiddish or Ladino and using Hebrew and Aramaic for liturgical purposes. When subsequent generations abandoned the first two languages, Hebrew and Aramaic were retained, used primarily for liturgy and rites of passage. Jewish American writers have often inserted Hebrew into their English texts by either reproducing the original alphabet or transliterating into Latin letters. This essay focuses on diverse strategies for representing liturgical Hebrew with an emphasis on the poetic, thematic, and sociolinguistic aspects of these expressions of both home and the foreign. Hebrew transliteration is discussed for its literary (rather than phonetic) rendering, for its multilingual creative contact with the other languages and cultures of each narrative. Among the authors whose works are discussed are Philip Roth, Michael Chabon, Nathan Englander, Joshua Cohen, Achy Obejas, and Gary Shteyngart.
Generic affiliation of Phyllagathis phamhoangii (Melastomataceae) from Vietnam
Authors: DAI JIN-HONG , ZHUANG QI-YUAN , ZHOU REN-CHAO , WAI JAREARNSAK SAE , DO TRUONG VAN , LIU YING
Published: November 2020

Phyllagathis phamhoangii, a species from Vietnam, was originally described in Phyllagathis based on its resemblance to P. nanakorniana and P. subrotunda in habit, rhizome morphology and leaf shape. However, its overall morphology, mainly stamen and capsule morphology, corresponds better with Fordiophyton indicating questionable generic affiliation. We included molecular (nrITS) and anatomical (crystal form) evidences to resolve the generic affiliation of P. phamhoangii. Our phylogenetic analyses recovered P. phamhoangii inside Fordiophyton and P. nanakorniana and P. subrotunda inside the Kerriothyrsus clade. The Fordiophyton clade is characterized by the presence of raphides, while the Kerriothyrsus clade is characterized by druses. Based on these evidences, P. phamhoangii is herein transferred to Fordiophyton, resulting in a new combination F. phamhoangii. It is morphologically similar to F. peperomiifolium but differs from the latter in the leaf blade with shortly acuminate to acuminate apex (vs. broadly acute), hypanthium 4-ridged (vs. not ridged), and connectives of shorter stamens dorsally spurred (vs. not spurred).
Begonia makuruyot (Begoniaceae, section Baryandra), a new species from Surigao del Norte Province, Philippines
Authors: RULE MARK GREGORY Q. , ANG YU PIN , RUBITE ROSARIO R. , DOCOT RUDOLPH VALENTINO A. , BUSTAMANTE RENE ALFRED ANTON , ROBINSON ALASTAIR S.
Published: November 2020

A new Begonia species, Begonia makuruyot, from B. section Baryandra is described and illustrated from forests over limestone in Surigao del Norte. This distinctive species, which appears to be endemic to the type locality, inhabits shaded limestone walls along the Daywan River at an elevation of 10–50 metres above sea level. Begonia makuruyot is distinguished from other Philippine Begonia by its rugose laminae, pendent leaves, pilose petioles and stipules fused with fleshy, aristate trichomes that are occasionally branching. A comparison with the phenetically similar B. acuminatissima is provided. Based on IUCN Red List criteria, B. makuruyot is designated Critically Endangered (CR).
Saussurea odorata (Asteraceae), a new species from western Mongolia

Authors: PYAK ELIZAVETA A. , PYAK ANDREI I. , MADYKA VIOLETTA V.
Published: November 2020

A new species of Asteraceae, Saussurea odorata, is described here based on morphological evidence. The new species was discovered in the southern part of the Mongolian Altai Mountains, Möst Sum (District), Khovd Aimag (Province), Mongolia. Morphological comparisons showed that S. odorata is similar to S. saichanensis and S. krylovii, but can be distinguished by its much-branched caudex, a larger number of capitula in a dense racemose synflorescence, and a strong odor due to the high density of glandular trichomes on both surfaces of leaves. Detailed illustrations, pictures of living plants, as well as a key for identification are presented.
Analysis of Debris Signature Characteristics and Evolution in the 24 May 2016 Dodge City, Kansas, Tornadoes
Authors: Wienhoff Zachary B. , Bluestein Howard B. , Reif Dylan W. , Wakimoto Roger M. , Wicker Louis J. , Kurdzo James M.
Published: November 2020

On 24 May 2016, a supercell that produced 13 tornadoes near Dodge City, Kansas, was documented by a rapid-scanning, X-band, polarimetric, Doppler radar (RaXPol). The anomalous nature of this storm, particularly the significant deviations in storm motion from the mean flow and number of tornadoes produced, is examined and discussed. RaXPol observed nine tornadoes with peak radar-derived intensities (ΔVmax) and durations ranging from weak (~60 m s−1) and short lived (<30 s) to intense (>150 m s−1) and long lived (>25 min). This case builds on previous studies of tornado debris signature (TDS) evolution with continuous near-surface sampling of multiple strong tornadoes. The TDS sizes increased as the tornadoes intensified but lacked direct correspondence to tornado intensity otherwise. The most significant growth of the TDS in both cases was linked to two substantial rear-flank-downdraft surges and subsequent debris ejections, resulting in growth of the TDSs to more than 3 times their original sizes. The TDS was also observed to continue its growth as the tornadoes decayed and lofted debris fell back to the surface. The TDS size and polarimetric composition were also found to correspond closely to the underlying surface cover, which resulted in reductions in ZDR in wheat fields and growth of the TDS in terraced dirt fields as a result of ground scouring. TDS growth with respect to tornado vortex tilt is also discussed.
Effects of post-infusion dwell on vacuum infusion of thermoset composites toughened by thermoplastic interlaminar veils
Authors: Shin Jung Hwan , Anders Mark , Kim Daniel , Jin Bo C , Nutt Steven
Published: November 2020

The effects of post-infusion dwell on vacuum infusion of thermoset composites toughened by non-woven thermoplastic interlaminar veils were investigated. Permeability measurements and simulation of the resin infusion process demonstrated that the toughening interlayers can effectively act as interlaminar flow distribution media. Local variations in permeability induced non-uniform flow fronts, resulting in high porosity. However, introduction of a low-temperature post-infusion dwell allowed more time for the resin to equilibrate pressure and redistribute during the post-filling stage, achieving full saturation of dry regions. The process parameters of the post-infusion dwell were determined using cure kinetics and viscosity models, while in situ process adjustments were implemented using dielectric cure monitoring system in conjunction with resin cure maps. Laminates fabricated with the modified cycle exhibited reduced porosity and greater peak load during impact testing. This work highlights potential advantages of the post-infusion dwell, which can similarly be applied to other vacuum infusion processes requiring a protracted post-filling stage.
Fabrication of polyvinyl alcohol based fast dissolving oral strips of sumatriptan succinate and metoclopramide HCL
Authors: Zaman Muhammad , Hassan Rabia , Razzaq Sobia , Mahmood Asif , Amjad Muhammad Wahab , Raja Maria Abdul Ghafoor , Qaisar Asif Ali , Majeed Abdul , Hanif Muhammad , Tahir Rana Azam
Published: November 2020

Migraine is a throbbing condition, usually associated with nausea and vomiting and requires concurrent administration of anti-migraine along with anti-emetic therapy. The current study was undertaken with an aim to fabricate fast dissolving oral strips (FDOSs) containing Sumatriptan succinate (anti-migraine) and Metoclopramide HCl (anti-emetic) in combination without involving any superdisintegrant. Hydrophilic polymer polyvinyl alcohol (PVA) was used alone with three concentrations of 100, 125, and 150 mg using variable concentrations of glycerol. The solvent casting technique was employed to formulate FDOSs and were evaluated for surface morphology, mechanical properties, surface pH, % moisture content, disintegration time (DT), total dissolving time (TDT), drug contents, and dissolution profile. PVA (150 mg) with 5% glycerol concentration gave best formulation results. FDOSs have exhibited good tensile strength with smooth and uniform surface morphology. DT was ranged from 7.7 to 28 s; while TDT was from 26.4 to 77.6 s. Both polymer and plasticizer concentrations were found to be influencing the characteristics of the strips. Dissolution studies were carried out in distilled water for 15 min and all the formulations have shown released more than 50% drug within first 2 min thereby highlighting the usefulness of FDOSs for the delivery of both drugs in combination significantly. Optimized combination of ingredients was found to be suitable for the formulation of FDOSs for simultaneous delivery of Metoclopramide HCl and Sumatriptan succinate.
Arming the troops: Post-translational modification of extracellular bacterial proteins
Authors: Forrest Suzanne , Welch Martin
Published: November 2020

Protein secretion is almost universally employed by bacteria. Some proteins are retained on the cell surface, whereas others are released into the extracellular milieu, often playing a key role in virulence. In this review, we discuss the diverse types and potential functions of post-translational modifications (PTMs) occurring to extracellular bacterial proteins.
Delirium on clozapine: A tale of friend turned foe-A case report
Authors: Das Aparna , Minner Rebecca , Krain Lewis , Spollen John
Published: November 2020

Treatment resistant schizophrenia (TRS) is often encountered in clinical practice. Clozapine remains the drug of choice in the management of TRS. Several studies have shown that clozapine is the most effective antipsychotic medication to date for TRS. But it is also well known that it has multiple side effects. Some side effects are transient and relatively benign, while other adverse effects are menacing, serious and life-threatening. Delirium may occur with clozapine and is a therapeutic challenge as there is always a risk of precipitating delirium on clozapine rechallenge. Limited management strategies are available as alternatives for the management of psychiatric illness stabilized on clozapine. In this case report, we describe an older adult patient who developed delirium on clozapine. The aims of this case report are to discuss the mechanism by which clozapine leads to delirium, revisit various factors which could possibly lead to delirium, and discuss the different management strategies available for management of psychiatric illness for a patient previously stabilized on clozapine.
Identity Distress, Parental Response, and Problem Behaviors in Juvenile Justice-Involved Boys
Authors: Barbot Baptiste , Hein Sascha
Published: November 2020

Youth involved with the juvenile justice system are not exempt from experiencing identity-related turmoil that is common during adolescence. Parents’ responses may exacerbate or mitigate this turmoil and, in turn, youth problem behaviors. Thus, this study investigated identity distress as a mediator of the relationship between parental response to adolescents’ distress and their problem behaviors among 113 detained males aged 12 to 18 ( Mage = 15.3, SD = 1.44) in Connecticut, USA. Participants completed measures of identity distress, parental response to their developmental distress, and multiple problem behaviors. A latent mediation model indicated that a supportive parental response was directly associated with decreased problem behaviors, whereas an avoidant parental response was indirectly associated with increased problem behaviors through increased identity distress. Developmentally salient identity-related distress of juveniles and the corresponding response of their parents are important to consider in understanding youth externalizing problem behaviors within the juvenile justice system.
Refinement of Climate-, Depth-, and Time-Based Laboratory Aging Procedure for Asphalt Mixtures
Authors: Braswell Elizabeth , Saleh Nooralhuda F. , Elwardany Michael , Yousefi Rad Farhad , Castorena Cassie , Underwood B. Shane , Kim Y. Richard
Published: November 2020

This paper refines the oxidation kinetics-based approach originally proposed in the NCHRP 09-54 project to determine the laboratory aging durations at 95°C that best reflect the effects of time, climate, and depth on loose asphalt mixtures. Aging durations that match the field aging at various pavement depths were determined in this study for asphalt mixtures, including warm-mix asphalt (WMA), polymer-modified asphalt (PMA), and reclaimed asphalt pavement (RAP). Here, the laboratory aging durations were used to calibrate a climatic aging index to prescribe the laboratory aging duration, given hourly pavement temperature history obtained from Enhanced Integrated Climatic Model analysis of the Modern Era Retrospective-Analysis for Research and Applications, Version 2 weather data. The recalibrated procedure determines the required laboratory aging durations with reasonable accuracy for virgin hot-mix asphalt (HMA) and WMA mixtures. From the recalibrated results, no variations were found with regard to the laboratory aging durations for WMA materials compared with HMA materials, but there were differences between the RAP and non-RAP mixtures. In some instances, the short-term aged RAP mixtures that were prepared according to AASHTO R 30 exceeded the aging level of 4-year-old field cores, suggesting that refinement of this standard short-term aging procedure may be necessary. Approximately half of the PMA sections evaluated exhibited outlier behavior that could have been caused by the unrealistically harsh thermal history of the field projects from which the cores were acquired.
Cellulose Nanocomposites for Performance Enhancement of Ordinary Portland Cement-Based Materials
Authors: Kamasamudram Kavya S. , Ashraf Warda , Landis Eric N.
Published: November 2020

Cellulose nanofibril (CNF) with a high aspect ratio, elastic modulus, tensile strength, and reactive surface area is a promising nanomaterial for improving the chemo-mechanical properties of cementitious matrixes. CNFs are typically less than 0.2 mm in length and 50 nm in width, and are extracted from plants and trees. This study investigated the potential application of three types of CNF for enhancing the performance of ordinary Portland cement (OPC) pastes: pure CNF (PCNF), silica coated CNF (SCNF), and lignin-containing CNF (LCNF). The performance of the cement pastes was monitored for cement paste workability, hydration kinetics, microstructural development, and mechanical performance (compressive strength and flexural strength). The dispersion stability of CNFs measured through zeta potential showed a better dispersion for SCNF when compared with PCNF and LCNF in varied alkaline mediums. The better stability of SCNF also resulted in improved workability of the cement paste mixtures containing this type of cellulose. All of the cellulose nanomaterials accelerated the cement hydration at the early stage as a result of the nucleation effect. Such an acceleration effect was slightly higher for SCNF because of the presence of silica nanoparticles. The addition of 0.1% SCNF increased the compressive strength (90 days) by 13% when compared with the control batch and 10% compared with the PCNF batch. The addition of 0.1% of PCNF enhanced the flexural strength by 70% followed by LCNF with 40% improvement. SCNF showed little to no effect on the flexural strength.
Emerging Therapies for Peanut Allergy
Authors: Hong Thomas S. , Hu Amy , Fahim Germin , Hermes-DeSantis Evelyn R.
Published: November 2020

Peanut allergy (PA) is a food allergy that causes an IgE-mediated type I hypersensitivity reaction. PA has become an increasing public health burden, with 2% of American children reported to have this condition in 2010. Current guidelines recommend allergen avoidance, patient education, and administration of H1 antihistamines, β2-agonists, or epinephrine based on the severity of reaction. In this review article, emerging therapies for PA are evaluated for their potential role in treating PA. Oral, epicutaneous, and sublingual immunotherapies have completed clinical trials with promising efficacy. In particular, Palforzia (AR101) is an oral immunotherapy that received Food and Drug Administration (FDA)-approval in January 2020 and Viaskin Peanut is an epicutaneous immunotherapy with an anticipated FDA decision date by August 5, 2020. Furthermore, adjuvant combinations with either probiotics or anti-IgE receptor antagonists have shown an improved efficacy and safety profile compared to oral immunotherapy alone. However, immunotherapy-induced adverse reaction rates are high due to the risks associated with intentional allergen exposure. These results suggest that peanut immunotherapy has a promising role in the treatment of PA, although further studies are needed before its incorporation into standard of care.
A cyclic-dependent vibration damping model of fiber-reinforced ceramic-matrix composites
Authors: Li Longbiao
Published: November 2020

Under cyclic fatigue loading, cyclic-dependent damage mechanisms affect the vibration damping of fiber-reinforced ceramic-matrix composites (CMCs). In this paper, a cyclic-dependent vibration damping model of fiber-reinforced CMCs is developed. Combining cyclic-dependent damage mechanisms, damage models and dissipated energy model, relationships between composite vibration damping, cyclic-dependent damage mechanisms, vibration stress and applied cycle number are established. Effects of material properties and damage state on composite vibration damping are analyzed for different applied cycle number and vibration stress. Experimental composite vibration damping of 2D and 3D C/SiC composites without/with coating is predicted for different vibration frequencies and applied cycle number. With increasing applied cycle number, cyclic-dependent composite vibration damping increases due to the increase ratio of interface debonding and slip. When fiber volume and matrix cracking spacing increase, cyclic-dependent composite vibration damping decreases due to the decrease ratio of interface debonding and slip.
Effect of infill pattern, density and material type of 3D printed cubic structure under quasi-static loading
Authors: Ma Quanjin , Rejab MRM , Kumar A Praveen , Fu Hao , Kumar Nallapaneni Manoj , Tang Jianbo
Published: November 2020

The present research work is aimed to investigate the effect of infill pattern, density and material types of 3D printed cubes under quasi-static axial compressive loading. The proposed samples were fabricated though 3D printing technique with two different materials, such as 100% polylactic acid (PLA) and 70% vol PLA mixed 30% vol carbon fiber (PLA/CF). Four infill pattern structures such as triangle, rectilinear, line and honeycomb with 20%, 40%, 60%, and 80% infill density were prepared. Subsequently, the quasi-static compression tests were performed on the fabricated 3D printed cubes to examine the effect of infill pattern, infill density and material types on crushing failure behaviour and energy-absorbing characteristics. The results revealed that the honeycomb infill pattern of 3D printed PLA cubic structure showed the best energy-absorbing characteristics compared to the other three infill patterns. From the present research study, it is highlighted that the proposed 3D printed structures with different material type, infill pattern and density have great potential to replace the conventional lightweight structures, which could provide better energy-absorbing characteristics.