bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase Ia/b, Open-Label, Multicenter Study of AZD4635 (an Adenosine A2A Receptor Antagonist) as Monotherapy or Combined with Durvalumab, in Patients with Solid Tumors
Authors: Lim Emerson A. , Bendell Johanna C. , Falchook Gerald S. , Bauer Todd M. , Drake Charles G. , Choe Jennifer H. , George Daniel J. , Karlix Janet L. , Ulahannan Susanna , Sachsenmeier Kris F. , Russell Deanna L. , Moorthy Ganesh , Sidders Ben S. , Pilling Elizabeth A. , Chen Huifang , Hattersley Maureen M. , Das Mayukh , Kumar Rakesh , Pouliot Gayle P. , Patel Manish R.
Published: August 2022

Purpose:

To evaluate AZD4635, an adenosine A2A receptor antagonist, as monotherapy or in combination with durvalumab in patients with advanced solid tumors.

Patients and Methods:

In phase Ia (dose escalation), patients had relapsed/refractory solid tumors; in phase Ib (dose expansion), patients had checkpoint inhibitor–naïve metastatic castration-resistant prostate cancer (mCRPC) or colorectal carcinoma, non–small cell lung cancer with prior anti–PD-1/PD-L1 exposure, or other solid tumors (checkpoint-naïve or prior anti–PD-1/PD-L1 exposure). Patients received AZD4635 monotherapy (75–200 mg once daily or 125 mg twice daily) or in combination with durvalumab (AZD4635 75 or 100 mg once daily). The primary objective was safety; secondary objectives included antitumor activity and pharmacokinetics; exploratory objectives included evaluation of an adenosine gene signature in patients with mCRPC.

Results:

As of September 8, 2020, 250 patients were treated (AZD4635, n = 161; AZD4635+durvalumab, n = 89). In phase Ia, DLTs were observed with monotherapy (125 mg twice daily; n = 2) and with combination treatment (75 mg; n = 1) in patients receiving nanosuspension. The most common treatment-related adverse events included nausea, fatigue, vomiting, decreased appetite, dizziness, and diarrhea. The RP2D of the AZD4635 capsule formulation was 75 mg once daily, as monotherapy or in combination with durvalumab. The pharmacokinetic profile was dose-proportional, and exposure was adequate to cover target with 100 mg nanosuspension or 75 mg capsule once daily. In patients with mCRPC receiving monotherapy or combination treatment, tumor responses (2/39 and 6/37, respectively) and prostate-specific antigen responses (3/60 and 10/45, respectively) were observed. High versus low blood-based adenosine signature was associated with median progression-free survival of 21 weeks versus 8.7 weeks.

Conclusions:

AZD4635 monotherapy or combination therapy was well tolerated. Objective responses support additional phase II combination studies in patients with mCRPC.
Clinical Validation of EndoPredict in Pre-Menopausal Women with ER-Positive, HER2-Negative Primary Breast Cancer
Authors: Constantinidou Anastasia , Marcou Yiola , Toss Michael S. , Simmons Timothy , Bernhisel Ryan , Hughes Elisha , Probst Braden , Meek Stephanie , Kakouri Eleni , Georgiou Georgios , Zouvani Ioanna , Savvidou Gabriella , Kuhl Vanessa , Doedt Jennifer , Wagner Susanne , Gutin Alexander , Slavin Thomas P. , Lanchbury Jerry S. , Kronenwett Ralf , Ellis Ian O. , Rakha Emad A.
Published: August 2022

Purpose:

The EndoPredict prognostic assay is validated to predict distant recurrence and response to chemotherapy primarily in post-menopausal women with estrogen receptor–positive (ER+), HER2− breast cancer. This study evaluated the performance of EndoPredict in pre-menopausal women.

Experimental Design:

Tumor samples from 385 pre-menopausal women with ER+, HER2− primary breast cancer (pT1-3, pN0-1) who did not receive chemotherapy in addition to endocrine therapy were tested with EndoPredict to produce a 12-gene EP molecular score and an integrated EPclin score that includes pathologic tumor size and nodal status. Associations of molecular and EPclin scores with 10-year distant recurrence–free survival (DRFS) were evaluated by Cox proportional hazards models and Kaplan–Meier analysis.

Results:

After a median follow-up of 9.7 years, both the EP molecular score and the molecular-clinicopathologic EPclin score were associated with increased risk of distant recurrence [HR, 1.33; 95% confidence interval (CI), 1.18–1.50; P = 7.2 × 10–6; HR, 3.58; 95% CI, 2.26–5.66; P = 9.8 × 10–8, respectively]. Both scores remained significant after adjusting for clinical factors in multivariate analysis. Patients with low-risk EPclin scores (64.7%) had significantly improved DRFS compared with high-risk patients (HR, 4.61; 95% CI, 1.40–15.17; P = 4.2 × 10–3). At 10 years, patients with low-risk and high-risk EPclin scores had a DRFS of 97% (95% CI, 93%–99%) and 76% (95% CI, 67%–82%), respectively.

Conclusions:

The EPclin score is strongly associated with DRFS in pre-menopausal women who received adjuvant endocrine therapy alone. On the basis of these data, pre-menopausal women with EPclin low-risk breast cancer may be treated with endocrine therapy only and safely forgo adjuvant chemotherapy.
High-Dimensional and Spatial Analysis Reveals Immune Landscape–Dependent Progression in Cutaneous Squamous Cell Carcinoma
Authors: Ferguson Angela L. , Sharman Ashleigh R. , Allen Ruth O. , Ye Thomas , Lee Jenny H. , Low Tsu-Hui H. , Ch'ng Sydney , Palme Carsten E. , Ashford Bruce , Ranson Marie , Clark Jonathan R. , Patrick Ellis , Gupta Ruta , Palendira Umaimainthan
Published: August 2022

Purpose:

The tumor immune microenvironment impacts the biological behavior of the tumor, but its effect on clinical outcomes in head and neck cutaneous squamous cell carcinomas (HNcSCC) is largely unknown.

Experimental Design:

We compared the immune milieu of high-risk HNcSCC that never progressed to metastasis with those that metastasized using multiparameter imaging mass cytometry. The cohort included both immunosuppressed patients (IS) and patients with an absence of clinical immune-suppression (ACIS). Spatial analyses were used to identify cellular interactions that were associated with tumor behavior.

Results:

Nonprogressing primary HNcSCC were characterized by higher CD8+ and CD4+ T-cell responses, including numerically increased regulatory T cells. In contrast, primary lesions from HNcSCC patients who progressed were largely devoid of T cells with lower numbers of innate immune cells and increased expression of checkpoint receptors and in the metastatic lesions were characterized by an accumulation of B cells. Spatial analysis reveals multiple cellular interactions associated with nonprogressing primary tumors that were distinct in primary tumors of disease-progressing patients. Cellular regional analysis of the tumor microenvironment also shows squamous cell–enriched tumor regions associated with primary nonprogressing tumors.

Conclusions:

Effective responses from both CD8+ and CD4+ T cells in the tumor microenvironment are essential for immune control of primary HNcSCC. Our findings indicate that the early events that shape the immune responses in primary tumors dictate progression and disease outcomes in HNcSCC.
Atezolizumab plus Bevacizumab in Patients with Unresectable or Metastatic Mucosal Melanoma: A Multicenter, Open-Label, Single-Arm Phase II Study
Authors: Mao Lili , Fang Meiyu , Chen Yu , Wei Xiaoting , Cao Jun , Lin Jing , Zhang Peng , Chen Ling , Cao Xiao , Chen Yujun , Guo Jun , Si Lu
Published: August 2022

Purpose:

Anti–programmed cell death-1 monotherapy is part of standard therapy for cutaneous melanoma but has low efficacy in mucosal melanoma. We evaluated the efficacy and safety of atezolizumab plus bevacizumab as first-line therapy for advanced mucosal melanoma.

Patients and Methods:

This multicenter, open-label, single-arm, phase II study used a Simon's two-stage design. Atezolizumab (fixed-dose, 1,200 mg) and bevacizumab (7.5 mg/kg) were administered by intravenous infusion every 3 weeks. The primary endpoint was objective response rate (ORR), determined per RECIST v1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety, with adverse events (AE) summarized using NCI-CTCAE v5.0.

Results:

Overall, 43 patients were enrolled, including 20 (46.5%) with unresectable and 23 (53.5%) with metastatic mucosal melanoma. Median follow-up was 13.4 months at data cutoff (July 30, 2021). Forty patients were evaluable for response: ORR was 45.0% [95% confidence interval (CI), 29.3%–61.5%; one complete response, 17 partial responses]. Median PFS was 8.2 months (95% CI, 2.7–9.6); 6- and 12-month PFS rates were 53.4% (95% CI, 36.6%–67.6%) and 28.1% (95% CI, 14.2%–43.9%), respectively. Median OS was not reached (NR; 95% CI, 14.4–NR). Six- and 12-month OS rates were 92.5% (95% CI, 78.5%–97.5%) and 76.0% (95% CI, 57.1%–87.5%), respectively. Median DOR was 12.5 months (95% CI, 5.5–NR). Overall, 90.7% (39/43) of patients experienced treatment-related AEs; 25.6% (11/43) experienced grade ≥3 events.

Conclusions:

Atezolizumab in combination with bevacizumab showed promising efficacy and manageable safety in patients with advanced mucosal melanoma.
Raptinal Induces Gasdermin E–Dependent Pyroptosis in Naïve and Therapy-Resistant Melanoma
Authors: Vernon Megane , Wilski Nicole A. , Kotas Daniel , Cai Weijia , Pomante Danielle , Tiago Manoela , Alnemri Emad S. , Aplin Andrew E.
Published: August 2022

Lack of response and acquired resistance continue to be limitations of targeted and immune-based therapies. Pyroptosis is an inflammatory form of cell death characterized by the release of inflammatory damage-associated molecular patterns (DAMP) and cytokines via gasdermin (GSDM) protein pores in the plasma membrane. Induction of pyroptosis has implications for treatment strategies in both therapy-responsive, as well as resistance forms of melanoma. We show that the caspase-3 activator, raptinal, induces pyroptosis in both human and mouse melanoma cell line models and delays tumor growth in vivo. Release of DAMPs and inflammatory cytokines was dependent on caspase activity and GSDME expression. Furthermore, raptinal stimulated pyroptosis in melanoma models that have acquired resistance to BRAF and MEK inhibitor therapy. These findings add support to efforts to induce pyroptosis in both the treatment-naïve and resistant settings.

Implications:

Raptinal can rapidly induce pyroptosis in naïve and BRAFi plus MEKi-resistant melanoma, which may be beneficial for patients who have developed acquired resistance to targeted therapies.
Laparotomy-Assisted 2-Port Fetoscopic Repair of Spina Bifida Aperta: Report of a Single-Center Experience in Paris, France
Authors: Arthuis Chloé , James Syril , Bussieres Laurence , Hovhannisyan Shushanik , Corroenne Romain , Ville Yves , Stirnemann Julien J.
Published: August 2022

Background: Given the maternal morbidity of open fetal surgery, the development of prenatal fetoscopic repair for spina bifida aperta (SBA) is encouraged. Objective: We hereby report the early results from our center, using a laparotomy-assisted CO2-fetoscopic approach. Methods: This study was conducted in patients with an SBA < T1 and >S1, <26 weeks of gestation, with Chiari II. Fetoscopic repair was performed using 2 operating trocars in the uterus exteriorized through a transverse laparotomy. Endoscopy was performed under humidified and heated CO2 insufflation. Following dissection of the lesion, a 1-layer approach was performed with a muscle/skin flap sutured over a patch of Duragen. Main outcomes were watertight repair at birth and the need for postnatal neurosurgical surgery including shunting within 6 months. Results: Of 87 women assessed for prenatal therapy, 7 were included. Surgery was performed at 24 (23–26) weeks’ gestation. There was no fetal demise. Conversion to hysterotomy was not performed, although surgery could not be performed in 1 case because of fetal position. Severe preeclampsia developed postoperatively in 1 case. In the other 6 cases, follow-up was uneventful except for premature rupture membranes which occurred in 3/6 cases at 30, 34, and 36+5 weeks’ gestation. Gestational age at delivery was 32 + 5 (31−36 + 5) weeks’ gestation. Repair was watertight at birth except in 2 cases which required complementary postnatal surgical repair. Reverse hindbrain herniation during pregnancy was observed in 4/6 cases. In 3/6 cases, shunting was necessary within 6 months after birth. At 12 months, a functional gain of ≥2 metameric levels was observed in 3 cases of the 6 survivors. Conclusion: Laparotomy-assisted fetoscopic repair is a reasonable option for women who choose and are eligible for antenatal surgery, both in terms of maternal and perinatal morbidity.
Atypical Biliary Adenofibroma of the Liver: Related Treatment and Performance
Authors: Liu Shao-Ru , Zhu Qi , Feng Ming-Bin , Yan Qing , Zhu Tai-Feng , Xu Lei-Bo
Published: August 2022

Biliary adenofibroma is an extremely rare benign liver tumor, but it may be a precancerous lesion of cholangiocarcinoma. So far, only 29 cases have been reported in the literature. A 30-year-old woman was admitted to our department for upper abdomen mass. The computed tomography scan showed a huge cystic and partly substantial mass between the left lobe of the liver and the descending duodenum, which was considered to be an exophytic tumor derived from the left lobe of the liver. Laparoscopic liver segment IVb resection and cholecystectomy were performed. Microscopic examination showed that the tumor was composed of glandular cavities of varying sizes and fibrous interstitium. The glandular cavity was covered with cubic or columnar epithelium without atypia. Some of the mesenchymal cells are myofibroblast-like and spindle-shaped with red-stained cytoplasm. The mesenchymal cells in some areas proliferate densely with moderate atypia. It was considered to be an atypical biliary adenofibroma with focal necrosis and active cell proliferation which may have malignant transformation potential. There was no recurrence and metastasis at a 6-month follow-up. Biliary adenofibroma is a rare benign tumor derived from the bile duct, but it may progress to malignancy and develop distant metastasis. It is difficult to distinguish it from other liver tumors through imaging examination and the gold standard of diagnosis is histopathological examination. Close clinical follow-up is recommended.
Direct and Indirect Effects of Blue Light Exposure on Skin: A Review of Published Literature
Authors: Suitthimeathegorn Orawan , Yang Cheng , Ma Yanyun , Liu Wei
Published: August 2022

The growing use of electronic devices and other artificial light sources in recent decades has changed the pattern of exposure to blue light (400–500 nm). Although some progress has been made in the study of the biological effects of blue light on the skin, many questions in this field remain unexplored. The aim of this article was to review the currently available evidence on the deleterious effects of blue light on the skin, as well as the methods and strategies designed to protect from the detrimental effects of blue light. PubMed and ProQuest databases were searched in January 2022. Search results were supplemented by articles considered relevant by the authors. The results of in vitro, in vivo and clinical studies show that blue light produces direct and indirect effects on the skin. The most significant direct effects are the excessive generation of reactive oxygen and nitrogen species, and hyperpigmentation. Reactive oxygen and nitrogen species cause DNA damage and modulate the immune response. Indirect effects of blue light include disruption of the central circadian rhythm regulation via melatonin signaling and local circadian rhythm regulation via direct effects on skin cells. Antioxidants and sunscreens containing titanium dioxide, iron oxides, and zinc oxide can be used to protect against the detrimental effects of blue light as part of a strategy that combines daytime protection and night-time repair. Blue light produces a wide variety of direct and indirect effects on the skin. As exposure to blue light from artificial sources is likely to continue to increase, this area warrants further investigation.
Comparative Metastatic Rates in GEP Class 1A versus 1B Posterior Uveal Melanoma: Results Contrary to Expectations
Authors: Augsburger James J. , Skinner Cassandra C. , Correa Zelia M.
Published: August 2022

Purpose: The purpose of this study was to determine whether the metastatic rates in patients with gene expression profile (GEP) class 1A versus 1B posterior uveal malignant melanoma supported or contradicted predictions of very low metastatic rate in GEP 1A cases and moderate rate in GEP 1B cases. Patients/Methods: 164 patients with a cytopathologically confirmed primary posterior uveal malignant melanoma classified by GEP testing as class 1 (100 GEP 1A, 64 GEP 1B) were evaluated. Kaplan-Meier rates of metastasis were computed and plotted for the GEP class 1 subgroups. Median follow-up of patients who were still alive without metastasis on the date of data analysis was 100.5 months for the GEP 1A patients and 97.2 months for the GEP 1B patients. Results: The actuarial 5-year rate of uveal melanoma metastasis was 10.8% (std. error = 3.2%) in the GEP 1A patients versus 0% in the GEP 1B patients, and the actuarial 10-year rate of metastasis was 12.2% (std. error = 3.5%) in the GEP 1A patients versus 2.1% (std. error 2.1%) in the GEP 1B patients. Conclusion: The results of this retrospective single-center study cast doubt on the validity of the prognostic stratification of GEP class 1 posterior uveal malignant melanomas into very low risk (GEP 1A) versus intermediate risk (GEP 1B) of metastasis subgroups provided by the commercially available GEP test.
A Discrepancy: Calcium Channel Blockers Are Effective for the Treatment of Hypertensive Left Ventricular Hypertrophy but Not as Effective for Prevention of Heart Failure
Authors: Koracevic Goran , Perisic Zoran , Stanojkovic Maja , Stojanovic Milovan , Zdravkovic Milos , Tomasevic Miloje , Djordjevic Dragan , Mladenovic Katarina , Koracevic Maja , Trkulja Jelena
Published: August 2022

Arterial hypertension (HTN) is important due to its high prevalence, morbidity, and mortality rates. Calcium channel blockers (CCBs) are the first-line antihypertensive drugs. HTN can lead to heart failure (HF) by causing hypertensive left ventricular hypertrophy (HTN LVH). CCBs are recommended for the treatment of HTN LVH. The aim of this study was to analyze the status of CCBs regarding (1) HTN LVH treatment and (2) capability to prevent HTN-induced HF in the guidelines. For this narrative review, the following databases were searched: Medline, Scopus, Science Direct, Springer, SAGE, Wiley, Oxford Journals, Cambridge, and Google Scholar. CCBs are effective antihypertensive drugs and a very good therapeutic option for HTN LVH as they can cause reverse LVH remodeling. Consequently, we may expect that CCBs would prevent HF. However, evidence suggests that CCBs confer less protection from HF than other first-line antihypertensive drugs. A negative inotropic action of nondihydropyridine CCBs may contribute to suboptimal protection against HF. This discrepancy is clinically relevant because CCBs are in one of the two recommended (single pill) combinations for the initial treatment of HTN. LVH is a strong risk factor for HF in HTN patients. When LVH arises, the risk of HF increases dramatically. CCBs are inferior to renin-angiotensin-aldosterone system blockers but still very effective in bringing about regression of HTN LVH; consequently, CCBs are expected to protect from HF. On the contrary, CCBs protect from HF less effectively than other first-line antihypertensive drugs. This discrepancy needs to be investigated further to improve clinical practice.
Excitatory Effects of Astrocytic Hydrogen Sulfide on the Electrical Activity of Oxytocin Neurons in the Supraoptic Nucleus
Authors: Wang Hongyang , Jiang Yunhao , Wang Xiaoran , Liu Haitao , Li Dongyang , Ling Shuo , Jia Shuwei , Liu Xiaoyu , Liu Yang , Hou Chunmei , Wang Yu-Feng
Published: August 2022

Introduction: In the regulation of oxytocin (OT) neuronal activity, hydrogen sulfide (H2S), a gaseous neurotransmitter, likely exerts an excitatory role. This role is associated with increased expression of astrocytic cystathionine-β-synthase (CBS), the key enzyme for H2S synthesis. However, it remains unclear whether H2S is mainly produced in astrocytes and contributes to the autoregulation of OT neurons. Methods: In hypothalamic slices of male rats, OT and H2S-associated drug effects were observed on the firing activity and spontaneous excitatory postsynaptic currents (sEPSCs) of putative OT neurons in the supraoptic nucleus (SON) in whole-cell patch-clamp recording. Expression of glial fibrillary acidic protein (GFAP) in the SON was analyzed in Western blots. In addition, changes in the length of rat pups’ hypothalamic astrocytic processes were observed in primary cultures. Results: In brain slices, OT significantly increased the firing rate of OT neurons, which was simulated by CBS allosteric agonist S-adenosyl-L-methionine (SAM) and H2S slow-releasing donor GYY4137 but blocked by CBS inhibitor aminooxyacetic acid (AOAA). L-α-aminoadipic acid (a gliotoxin) blocked SAM-evoked excitation. OT and SAM also increased the frequency and amplitude of sEPSCs; the effect of OT was blocked by AOAA. Both OT and GYY4137 reduced GFAP expression in the SON. Morphologically, OT or GYY4137 time-dependently reduced the length of astrocytic processes in primary cultures. Conclusions: These findings indicate that the auto-excitatory effect of OT on OT neurons is mediated by H2S from astrocytes at least partially and astrocytic H2S can elicit retraction of astrocytic processes that subsequently increase OT neuronal excitability.
Memoria y juvenicidio en el estallido social de Colombia (2021)
Authors: Aguilar-Forero Nicolás
Published: August 2022

(analítico)¿Cómo se relacionaron la memoria y el juvenicidio en el contexto del paro nacional de 2021 en Colombia? El presente artículo responde esta pregunta por medio de un estudio que combinó el activismo en las calles con el análisis de los registros que los jóvenes dejaron en la red. Se participó en varias de las jornadas del paro nacional en Bogotá y se analizaron las publicaciones que, entre el 28 de abril y el 2 de junio de 2021, realizó el colectivo Escudos Azules en Twitter. Los resultados evidencian que la memoria y el juvenicidio convergieron en un conjunto de acciones colectivas en las que, a través de distintos ejercicios de memoria, los jóvenes confrontaron el juvenicidio sistemáticomediante el cual se han eliminado, criminalizado y estigmatizado sus prácticas políticas.
Palabras clave: Memoria; participación juvenil; violencia; juvenicidio; Colombia.
Juvenicidio: un concepto parido por el dolor. Reflexiones desde una revisión bibliográfica
Authors: Bonvillani Andrea
Published: August 2022

(analítico)Para analizar núcleos de discusión teórica y estado de avance de investigaciones en el campo del juvenicidio, se presenta una revisión cualitativa sistemática de literatura científica en español publicada entre 2010 y 2021. Los resultados muestran que, frente al dolor que produce la muerte violenta y sistemática de jóvenes, su aporte fundamental es conceptualizarla como crimen bajo responsabilidad estatal, potencial encuadre jurídico de demandas en esa arena. Particularmente en los últimos cuatro años, su aplicación ha posibilitado trazar un mapa de procesos de violencia contra jóvenes latinoamericanos en enclaves geopolíticos e históricos situados, así como de estrategias de resistencias en defensa de la vida. La discusión crítica identificó como áreas de vacancia estudios empíricos sobre dimensiones subjetivas-emocionales del padecimiento de las víctimas y su incidencia en políticas públicas.
Palabras clave: Jóvenes; violencia; movimientos juveniles; investigación.
Management of Infective Endocarditis in People Who Inject Drugs: A Scientific Statement From the American Heart Association
Authors: Baddour Larry M. , Weimer Melissa B. , Wurcel Alysse G. , McElhinney Doff B. , Marks Laura R. , Fanucchi Laura C. , Esquer Garrigos Zerelda , Pettersson Gosta B. , DeSimone Daniel C. ,   on behalf of the American Heart Association Rheumatic Fever, Endocarditis and Kawasaki Disease Committee of the Council on Lifelong Congenital Heart Disease and Heart Health in the Young; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; and Council on Peripheral Vascular Disease
Published: August 2022

Background:

The American Heart Association has sponsored both guidelines and scientific statements that address the diagnosis, management, and prevention of infective endocarditis. As a result of the unprecedented and increasing incidence of infective endocarditis cases among people who inject drugs, the American Heart Association sponsored this original scientific statement. It provides a more in-depth focus on the management of infective endocarditis among this unique population than what has been provided in prior American Heart Association infective endocarditis–related documents.

Methods:

A writing group was named and consisted of recognized experts in the fields of infectious diseases, cardiology, addiction medicine, and cardiovascular surgery in October 2021. A literature search was conducted in Embase on November 19, 2021, and multiple terms were used, with 1345 English-language articles identified after removal of duplicates.

Conclusions:

Management of infective endocarditis in people who inject drugs is complex and requires a unique approach in all aspects of care. Clinicians must appreciate that it requires involvement of a variety of specialists and that consultation by addiction-trained clinicians is as important as that of more traditional members of the endocarditis team to improve infective endocarditis outcomes. Preventive measures are critical in people who inject drugs and are cured of an initial bout of infective endocarditis because they remain at extremely high risk for subsequent bouts of infective endocarditis, regardless of whether injection drug use is continued.
Terminology for a FAIR Framework for the Virus Outbreak Data Network-Africa
Authors: Plug Ruduan , Liang Yan , Aktau Aliya , Basajja Mariam , Oladipo Francisca , van Reisen Mirjam
Published: August 2022

The field of health data management poses unique challenges in relation to data ownership, the privacy of data subjects, and the reusability of data. The FAIR Guidelines have been developed to address these challenges. The Virus Outbreak Data Network (VODAN) architecture builds on these principles, using the European Union's General Data Protection Regulation (GDPR) framework to ensure compliance with local data regulations, while using information knowledge management concepts to further improve data provenance and interoperability. In this article we provide an overview of the terminology used in the field of FAIR data management, with a specific focus on FAIR compliant health information management, as implemented in the VODAN architecture.
Possibility of Enhancing Digital Health Interoperability in Uganda through FAIR Data
Authors: Basajja Mariam , Nambobi Mutwalibi , Wolstencroft Katy
Published: August 2022

The digital health landscape in Uganda is plagued by problems with interoperability and sustainability, due to fragmentation and a lack of integrated digital health solutions. This can be partly attributed to the absence of policies on the interoperability of data, as well as the fact that there is no common goal to make digital data and data infrastructure interoperable across the data ecosystem. The promulgation of the FAIR Guidelines in 2016 brought together various data stewards and stakeholders to adopt a common vision on data management and enable greater interoperability. This article explores the potential of enhancing digital health interoperability through FAIR by analysing the digital solutions piloted in Uganda and their sustainability. It looks at the factors that are currently hindering interoperability by examining existing digital health solutions in Uganda, such as the Digital Health Atlas Uganda (DHA-U) and Uganda Digital Health Dashboard (UDHD). The level of FAIRness of the two dashboards was determined using the FAIR Evaluation Services tool. Analysis was also carried out to discover the level of FAIRness of the digital health solutions within the dashboards and the most frequently used software applications and data standards by the different digital health interventions in Uganda.
Three circles and a few promises
Authors: Fakhro Elham , Mallat Chibli
Published: August 2022

The chapter introduces the volume on constitutionalism in the Arab Gulf states. It situates the development of national constitutionalism against three backdrops: the global constitutional realm, the regional Middle East system, and the Gulf sub-region. It considers the integration of Gulf constitutions in the global study of constitutionalism by emphasizing that these texts – while often highly circumscribed – ought to be examined as the expression of an evolving balance of powers between ruler and ruled. The chapter reflects on common themes underlying Arab Gulf constitutional development, including the rise of social movements in many states calling for parliamentary representation, the continued domination of monarchies on all branches of government, and the budding but limited role of courts. It sets these themes against the mostly unyielding commitment by Rulers to a mode of governance that is (i) monarchical, (ii) conservative, (iii) centralized, (iv) monolithic and (v) patriarchal, and which appears to contradict some of the very basis of constitutionalism. A final section draws on the historic roots of the promise of istiham, translated as voting, a concept developed in the Ahkam sultaniyya of Abu Ya‘la’s, an 11th century Hanbali jurist, as an alluring harbinger of the right to vote for the political leader of the community.
Kuwait: The First Arab Gulf Constitutionalism
Authors: Ghabra Shafeeq , Alterkait Tahani
Published: August 2022

This chapter provides a historical overview of Kuwait’s constitutional system. It begins by analysing the tradition of joint consultation in Kuwait before turning to three institutions that proved central to the formation of its contemporary constitutional system: the 1921 Shura Council, the 1938 Legislative Council, and the 1962 Constituent Council (the body that drafted Kuwait’s constitution). It relies on archival sources of the Kuwait National Assembly to bring to light the internal workings of the Constituent Council and the central discussions taking place within it, including over the role of Islamic law and democracy. The chapter explores recent pressures on the system, culminating in the 2011 Arab Spring protests and the subsequent ‘four votes five districts’ ruling by Kuwait’s Constitutional Court, in 2012. It explains how Kuwait’s hybrid system incorporates elements of monarchism and parliamentarianism, and makes the case for its continued reform to meet the democratic aspirations of the people of Kuwait.
Qatar: Constitutional Challenges
Authors: Al-Sayed Hassan Abdulrahim
Published: August 2022

This chapter examines the development of Qatar’s constitutional system. It is divided into two main sections. The first is historic: it describes Qatar’s political and constitutional system under British authority, under the Provisional Basic Law of 1970 (‘the Provisional Basic Law’), and under the amended Provisional Basic Law of 1972 (‘the Amended Provisional Basic Law’). The second section examines the events leading up to the passage of a permanent Constitution in 2004 (the ‘2004 Constitution’, or the ‘Permanent Constitution’), and in this section we learn about the scope of the democratic system and the principle of separation of powers stipulated in the Constitution. This section analyzes the main provisions of this text. It shows that while the 2004 Constitution provides for the transformation of Qatar’s fully appointed Advisory Council (the ‘Council’ or ‘Shura Council’) into a partially elected legislative body, these provisions were not enforced until the Shura Council elections of October 2021.

The chapter details how the 2004 Constitution created important changes by permitting – for the first time – the judiciary to exercise competence over administrative and constitutional matters. As a result, Qatar has established specialized administrative districts in the Court of First Instance and the Court of Appeal that exercise oversight over some government agencies. Yet even in this area, progress has been uneven. Although courts are empowered to exercise judicial review, specific areas of redress are deemed non-justiciable. In addition, provisions related to the development of a constitutional court remain un-activated. The chapter will also examine the Shura Council elections that took place in October 2021, and related events.
Saudi Arabia: Literal Islamic Constitutionalism
Authors: Mallat Chibli
Published: August 2022

The article describes in a first part the legal underpinnings of the absolute monarchy under the basic laws of government passed in 1992 and the iteration of Majlis al-shura, the parliament-like institution in the Kingdom, which is subordinated to the executive in various ways. It examines in a second part some core human values defined universally in the light of court cases. Dissent in the form of freedom of expression and right to demonstrate, as well as the punishment of dissent in capital punishment cases, form the main focus for the discussion in this latter section.
The United Arab Emirates: Forging Federalism
Authors: Nasrallah Faris
Published: August 2022

This chapter provides a broad overview of the United Arab Emirates’ (‘UAE’) federal constitution. Through a qualitative analysis of Federal Supreme Court (‘FSC’) data, it provides insight into how the UAE’s judicial system maintains a balance of power between central and federal authorities. Further, it shows how the FSC utilizes a judicial practice of constitutional code-switching to preserve policy and polity stability. This chapter also examines the FSC’s operation within a multi-layered system of laws and customs, to pursue a harmonised federal system that enshrines relatively high degrees of federal autonomy, upholds principles of shariʿa, and supports the UAE’s position as a haven for global capital. Lastly, this chapter also explores limits in the FSC’s ability to act as a mechanism for accountability by restraining jurisdiction over matters involving disciplinary and criminal actions taken against senior public officials.
Constitutional Courts in Arab Gulf States
Authors: Waheedi Salma
Published: August 2022

This chapter explores constitutional review in the two GCC states that have developed judicial bodies empowered to conduct judicial review: Kuwait and Bahrain. The chapter begins by describing the constitutional frameworks of Kuwait and Bahrain and the main features of their judicial review models, embodied in their respective constitutional court laws and other legislation pertaining to the judiciary. It then moves to an examination of the legal and institutional designs that enable or limit the independent exercise of judicial oversight by these constitutional courts. Finally, the chapter presents an analysis of constitutional rulings that illustrate the broad features of each court’s jurisprudence. It concludes with a reflection on lingering political and structural challenges to their full exercise of independent constitutional review in both states.
How to be Great (Britain)? Discourses of Greatness in the United Kingdom’s Referendums on Europe
Authors: Rogstad Adrian , Martill Benjamin
Published: August 2022

This article analyses the discursive constitution and contestation of British ‘greatness’ during the campaigns for the 1975 referendum on UK membership of the European Communities and the 2016 referendum on membership of the European Union. It finds that ideas about British greatness formed a central part of the discourse on Britain’s role in the world on both sides in each campaign, joining recent literature on Brexit challenging the view that greatness has been primarily a right-wing preoccupation. By demonstrating the existence of distinct yet overlapping discourses of greatness, the article also adds nuance to accounts of the centrality of greatness to British foreign policy identity. The article employs a discourse-theoretical approach to uncover the central discursive ‘nodal points’ and the ‘floating signifiers’ of greatness claimed by each side. Empirically, it draws on a collection of campaign materials from both referendums.
Globalisation, Divided Societies and Nation-Centred Economic Policies in America and Britain
Authors: Schirm Stefan A.
Published: August 2022

A stronger emphasis on domestic politics and national sovereignty has recently shaped international economic relations, for instance, in the United Kingdom and the United States. This trend weakened the liberal international economic order (lio) with its promotion of globalisation and multilateralism. Why have the UK and the US, which formerly spearheaded the liberal order, embraced nation-centred foreign economic policies (ncp) under the Trump and Johnson governments? I argue that domestic forces predominantly drove this shift, since a political de facto alignment of value-based societal ideas and material interests increasingly favoured national self-determination and the privileging of domestic groups. The negative consequences of the lio such as rising income inequality, job losses and a perceived heteronomy had strengthened societal ideas and interests that converged in support of ncp. I examine these arguments by applying the societal approach to governmental preference formation in case studies on Johnson’s Brexit policy and Trump’s trade policy towards China.
On a Path towards Forgiveness: Garden-Practices and Aesthetics of Engagement in Tan Twan Eng’s
Authors: Pradittatsanee Darin
Published: August 2022

This paper examines the human-nature relationship in the art of Japanese gardening in Tan Twan Eng’s The Garden of Evening Mists (2012). Drawing upon the aesthetics of Japanese gardening and theories of garden art, it argues that the novel advocates the complementarity of nature and human artifice in gardening. Japanese gardening which is related to the Taoist concept of yinyang and the Buddhist notion of impermanence, together with its principle of shakkei (borrowed landscape), suggests a combination of anthropocentric and ecocentric relationships with nature. Moreover, since Japanese aesthetics is interwoven with ways of living, the paper examines how the female protagonist’s apprenticeship to a Japanese gardener in the Cameron Highlands of Malaya gradually alters her mind and opens up ways of coping with her traumatic experience, during the Occupation, in a Japanese internment camp. It argues that gardening art, what art philosopher Arnold Berleant calls the “aesthetics of engagement,” and changing gardenscape induce the protagonist to comprehend impermanence, moral ambiguity and the complementary co-existence of memory and forgetting, all of which enable her to forgive the Japanese transgressors and to make peace with the past.
A new species of deep-sea anglerfish, genus Himantolophus (Lophiiformes: Himantolophidae) from the Andaman Sea, India
Authors: RAJEESHKUMAR MELEPPURA , PIETSCH THEODORE W. , SARAVANANE NARYANANE
Published: August 2022

A new species of the deep-sea ceratioid anglerfish genus Himantolophus is described from a single specimen collected off the east coast of the northern Andaman and Nicobar Islands, India, a member of the Himantolophus albinares-group, based in part on the absence of anterior escal appendages. The new species differs from other members of this group in having a unique illicial and escal morphology with a simple basimedial and a pair of basilateral filaments on the esca. The new species is compared with previously recognized members of the H. albinares-group.
A Numerical Study of Downbursts Using the BLASIUS Model
Authors: Liu Hongchao , Huang Qian , Chou Yan , Tian Hongying , Zhang Yunshuai , Wu Xixi , Zhang Junxia , Wang Minzhong
Published: August 2022

Downbursts can produce severe damage in near-ground areas and can also pose serious threats to aircraft in flight. In this study, a high-resolution boundary layer model—the Boundary Layer Above Stationary, Inhomogeneous Uneven Surface (BLASIUS) model—is used to simulate the evolution of a downburst. The observational data collected in Tazhong, China, located in hinterland of the Taklimakan Desert, during the Boundary Layer Comprehensive Observational Experiment on 27 July 2016 are used as the thermodynamic initial field for the BLASIUS model. In addition, the impacts of the terrain on the structure, turbulence intensity, and maximum wind speed of the downburst are also investigated. The results show that the BLASIUS model can simulate the structure and evolution characteristics of downbursts. The cold pool becomes warm if an isolated hill is implanted in the model under the same model conditions. Both the movement speed of the head and the average wind speed of the downburst decrease, while the maximum wind speed increases. The scale of the hill affects the dynamic and thermodynamic structures of the downburst through obstruction and entrainment mixing. The maximum wind speeds occur on the windward slope, and the downburst passes over the hill in the various tests with a hill. The head of the cold pool becomes narrow and tall for larger hill width cases. The Froude number generally decreases as the height of the hill increases, and the downburst can pass over the hill. The results are helpful to improve our understanding of the effects that terrain blocking on downburst structure and near-ground wind shear.

Significance Statement

Downbursts have the potential to cause significant damage to building structures and agricultural production and to cause unpredictable serious disasters. It is particularly important to understand the structure and evolution of downbursts. In addition, the influence of the topography on the structure and intensity of turbulent vortices during a downburst remain unclear. The results show that the Boundary Layer Above Stationary, Inhomogeneous Uneven Surface (BLASIUS) model can simulate the structure and evolution characteristics of downbursts. The cold pool becomes warm if an isolated hill is implanted in the model. The scale of the hill affects the dynamic and thermodynamic structures of the downburst through obstruction and entrainment mixing. The Froude number generally decreases as the height of the hill increases, and the downburst can pass over the hill.
Influences of Spring Land Surface Thermal Anomalies over West Asia on Indian Early Summer Monsoon Activity and Its Pathway
Authors: Yang Jingqiu , Chen Haishan
Published: August 2022

Exploring the premonsoonal land thermal predictor of the Indian summer monsoon is a hot topic under the background of global warming, and West Asia is one of the regions with the most significant warming in spring. In this study, we investigated the impact of anomalous spring land surface warming over West Asia on early summer (June) Indian monsoon precipitation as well as its possible mechanisms based on statistical analysis and numerical simulations. It has been found that spring land surface anomalous warming over West Asia corresponds to the enhancement of the leading mode of early summer precipitation in the Indian subcontinent, especially in its northern part. Further analysis indicates that an anomalously warm land surface over West Asia can advance the transition of atmospheric conditions toward the warm season by heating the atmosphere above. The increased land–sea meridional thermal contrast favors the intensification of the low-level jet and monsoon trough, further inducing anomalous moisture convergence and ascending motion over northern India. Additionally, the heat-driven anomalous upper-tropospheric anticyclone over West Asia favors the intensification of the tropical easterly jet and the northwestward development of the South Asian high (SAH). The enhanced SAH dynamically couples with the lower- to middle-level cyclonic circulation over northern India, resulting in a stronger monsoon and increased precipitation. These findings are helpful for better understanding and prediction of Indian early summer monsoon.

Significance Statement

The land surface thermal condition is critical to the monsoon activity and exploring the premonsoonal land thermal predictor of Indian summer monsoon remains a hot topic. The purpose of this study is to explore how spring land surface thermal anomalies over West Asia impact Indian monsoon activity in early summer (June). The anomalous land surface warming over West Asia can lead to a stronger Indian monsoon in early summer by heating and driving the atmosphere, which benefits the precipitation increase over northern India. Our results provide a further scientific basis for the prediction of early summer Indian precipitation.
Effect of Plastic Bag Extraction in Minimally Invasive Appendectomy
Authors: Moisés De Almeida Leite Rodrigo , de Souza Alexandre Venancio , Cauley Christy , Goldstone Rob , Francone Todd , Bay Camden P. , Ricciardi Rocco
Published: August 2022

Background

Evidence regarding the effects of plastic bag use for appendix removal during minimally invasive appendectomy remains scarce and conflicting.

Objective

This study aimed to analyze the effects of plastic bag use during minimally invasive appendectomy on preoperative infection risk, morbidity and mortality.

Design

This retrospective analysis of the prospective National Surgical Quality Improvement Program (NSQIP) cohort program.

Setting

This study included data from the NSQIP database between the years of 2016 and 2019.

Patient

Adult patients undergoing minimally invasive (laparoscopic or robotic) without unplanned conversion to open surgery.

Intervention

Use of plastic bag for specimen removal during appendectomy.

Main Outcome Measures

Risk ratios for the incidence of superficial surgical site infection, intra-abdominal abscess, overall medical morbidity, and overall mortality.

Results

There were 43 783 cases of minimally invasive appendectomy in the NSQIP database between the years of 2016 and 2019. Among those who reported information regarding use of plastic bag, 28 589 (91.87%) reported use of plastic bag for specimen removal. Use of plastic bag was associated with a significant decrease in superficial surgical site infection (RR .39 (95% CI: .31-.49), P < .001), and in the risk of postoperative intra-abdominal abscess (RR: 0.66 (.57-.77), P < .001)). We also observed a robust reduction in overall medical-related morbidity and overall mortality, even after adjusting for multiple confounders.

Limitations

Observational nature of the study cannot exclude residual bias. Also, there was a significant rate of missing values for plastic bag use, which may bias results.

Conclusions

In this global prospective cohort using NSQIP database, use of plastic bag for appendix removal during minimally invasive appendectomy was associated with a significant improvement in surgical related outcomes and reduction in morbidity and overall mortality.
Neck swelling 19 days after thyroidectomy: A case report of a rare chyle leak patient
Authors: Pan Huili , Jin Peile , Cao Jun , Yang Yan
Published: August 2022

The occurrence of chyle leak after neck dissection for thyroid carcinoma is uncommon, but it usually occurs within 1–10 days after surgery. We encountered a 30-year-old patient with chyle leak 19 days after the operation for thyroid carcinoma. The initial symptom was swelling of the neck, which was quickly diagnosed as chyle leak by puncture. This report describes the patient’s presentation and discusses the conservative management of this complication. We highlight that more attention should be given to chyle leak in high-risk patients, and stricter dietary management for these patients after surgery may avoid this complication. In addition, timely diagnosis and rapid implementation of various conservative treatment measures play an important role in patient recovery.