bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors Associated with Durable Progression-Free Survival in Patients with Relapsed or Refractory Multiple Myeloma Treated with Anti-BCMA CAR T-cell Therapy
Authors: Zhang Mingming , Zhou Linghui , Zhao Houli , Zhang Yanlei , Wei Guoqing , Hong Ruimin , Wu Wenjun , Xu Huijun , Wang Linqin , Ni Fang , Cui Jiazhen , Peng Shuixiu , Huang Chih-Hua , Chang Alex H. , Hu Yongxian , Huang He
Published: September 2021

Purpose:

B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy results in high remission rates in patients with relapsed/refractory (R/R) multiple myeloma. However, the factors associated with prognosis following CAR T-cell therapy are unknown.

Patients and Methods:

Between July 1, 2018 and July 31, 2020, 61 patients with R/R multiple myeloma received anti-BCMA CAR T-cell therapy (Chictr.org number, ChiCTR1800017404). Step-wise multivariate Cox regression and competing risk analyses were conducted to identify poor prognosis–associated risk factors.

Results:

Sixty patients (98.4%) experienced cytokine release syndrome (CRS), including 33, 23, and 4 cases of CRS grades 1 to 2, 3, and 4, respectively. The objective response rate (ORR) was 98.3%, and the complete remission (CR) rate was 70.3%. With a median follow-up period of 21.1 months, the 1-year overall survival (OS) and progression-free survival (PFS) rates were 78.0% and 50.2%, respectively. The median PFS was 12.7 months. Cox modeling revealed that poor PFS was associated with extramedullary disease [HR = 2.59, 95% confidence interval (95% CI) = 1.29–5.21, P = 0.008], light chain multiple myeloma (HR = 2.53, 95% CI = 1.03–5.97, P = 0.035), high-risk cytogenetics (HR = 2.80, 95% CI = 1.27–6.14, P = 0.01), and prior treatment with more than 3 therapeutic lines (HR = 3.14, 95% CI = 1.34–7.34, P = 0.008). Among the 41 CR cases, competing risk analyses demonstrated higher relapse predispositions in those with extramedullary disease (HR = 4.51, 95% CI = 1.86–10.9, P = 0.001), light chain multiple myeloma (HR = 4.89, 95% CI = 1.52 – 15.7, P = 0.008), or high-risk cytogenetics (HR = 5.09, 95% CI = 1.63–15.9, P = 0.005).

Conclusions:

Anti-BCMA CAR T-cell therapy is safe and effective for R/R multiple myeloma. For patients with high-risk factors, improvements to extend remission and more specific individualized therapies are needed.
Changes in PPAR-γ Expression Are Associated with microRNA Profiles during Fetal Programming due to Maternal Overweight and Obesity
Authors: Gaytán-Pacheco Noemí , Lima-Rogel Victoria , Méndez-Mancilla Alejandro , Escalante-Padrón Francisco , Toro-Ortíz Juan Carlos , Jiménez-Capdeville María Esther , Zaga-Clavellina Verónica , Portales-Pérez Diana P. , Noyola Daniel E. , Salgado-Bustamante Mariana
Published: September 2021

Background: There has been a global increase in the prevalence of obesity in pregnant women in recent years. Animal studies have shown that intrauterine environment associated with maternal obesity leads to epigenetic changes. However, the effects of epigenetic changes occurring before birth in response to maternal conditions have not been clearly characterized in humans. Objective: The aim of the study was to analyze peroxisome proliferator-activated receptor (PPAR)-γ expression in cell cultures from newborns from mothers with overweight and obesity, in response to in vitro metabolic challenges and their relationship with microRNA profile and cytokine expression. Methods/Study design: The profile of circulating microRNAs from 72 mother-child pairs (including healthy infants born to normal weight [n = 35], overweight [n = 25], and obese [n = 12] mothers) was determined through real-time PCR, and the PPAR-γ expression in peripheral blood mononuclear cell cultures from offspring was analyzed after in vitro challenges. Results: miR-146a, miR-155, and miR-378a were upregulated in overweight mothers, while miR-378a was upregulated in obese mothers compared to normal weight mothers. In children from overweight mothers, miR-155 and miR-221 were downregulated and miR-146a was upregulated, while offspring of mothers with obesity showed downregulation of miR-155, miR-221, and miR-1301. These microRNAs have direct or indirect relation with PPAR-γ expression. In vitro exposure to high triglyceride and exposure to miR-378a induced a higher expression of PPAR-γ in cells from offspring of mothers with overweight and obesity. In contrast, cells from offspring of mothers with obesity cultured with high glucose concentrations showed PPAR-γ downregulation. IL-1ß, IL-6, and TNF-α expression in cells of offspring of overweight and obese mothers differed from that of offspring of normal weight mothers. Limitation of our study is the small sample size. Conclusion: The blood microRNA profile, and in vitro PPAR-γ and inflammatory cytokine expression in cells of newborn infants are associated with maternal obesity indicating that epigenetic marks may be established during intrauterine development. Key Message: Neonatal microRNA profile is associated with maternal weight. Neonatal microRNA profile is independent of maternal microRNA profile. PPAR-γ expression in newborn cell cultures is affected by maternal weight
TERT Promoter Mutational Status in the Management of Cutaneous Melanoma: Comparison with Sentinel Lymph Node Biopsy
Authors: Martins Francisco , Martins César , Fernandes Margarida Sá , Andrade Maria Isabel , Lopes José Manuel , Soares Paula , Pópulo Helena
Published: September 2021

Background: While BRAF mutations seem important for early melanomagenesis, mutations in the TERT promoter (TERTp) are related to metastasis. Yet, in conventional melanoma management, risk stratification does not depend on molecular biomarkers that can indicate the stage of progression, but rather on clinical, pathological, sentinel lymph node (SLN), and radiologic evaluation. The aim of this work was to evaluate the frequency and prognostic impact of TERTp mutations, comparing their predictive value to those of conventional procedures in melanoma management. Methods: Mutational analysis of a series of 91 cases was performed. The correlations between TERTp and BRAF mutational status and clinicopathological features were assessed. Results: The mutation rate was 33% for TERTp and 30% for BRAF. There was 68% concordance between primary and metastatic samples for TERTp mutations and 92% for BRAF mutations. TERTp mutations are significantly associated with the presence of BRAF mutations, features of worse prognosis, and a reduced disease-free survival. Also, TERTp mutational status was similar to SLN biopsy as a predictive factor of cutaneous melanoma recurrence and metastasis. Conclusions: The predictive value of TERTp mutations may be similar to that of SLN biopsy and its integration in the management algorithm of melanoma patients should be considered.
Perioperative Outcomes of Holmium Laser Enucleation of the Prostate: A Systematic Review
Authors: Porreca Angelo , Colicchia Michele , Tafuri Alessandro , D’Agostino Daniele , Busetto Gian Maria , Crestani Alessandro , Odorizzi Katia , Amigoni Nelia , Rizzetto Riccardo , Gozzo Alessandra , Gallina Sebastian , Bianchi Lorenzo , Ferro Matteo , Falabella Roberto , Romagnoli Daniele , Antonelli Alessandro , Corsi Paolo , Schiavina Riccardo
Published: September 2021

Introduction: The aim of the study was to systematically review the literature and describe perioperative complications of holmium laser enucleation of the prostate (HoLEP), including the Clavien-Dindo classification of surgical complications. Methods: All English language publications on HoLEP were evaluated. We followed the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) guidelines to evaluate PubMed®, Scopus®, and Web of Science™ databases from January 1, 1998, to June 1, 2020. Results: Fifty-seven studies were included, for a total of 10,371 procedures. We distinguished between intra-, peri-, and postoperative complications. Overall, the rate of complications is 0–7%. Intraoperative complications include incomplete morcellation (2.3%), capsular perforation (2.2%), bladder (2.4%), and ureteric orifice (0.4%) injuries. Perioperative complications include postoperative urinary retention (0.2%), hematuria and clot retention (2.6%), and cystoscopy for clot evacuation (0.7%). Postoperative complications include dysuria (7.5%), stress (4.0%), urge (1.8%), transient (7%) and permanent (1.3%) urinary incontinence, urethral stricture (2%) and bladder neck contracture (1%). Conclusions: HoLEP is a safe procedure, with a satisfactory low complication rate. The most common reported perioperative complications are not severe (Clavien-Dindo classification grades 1–2). Further randomized studies are certainly warranted to fully determine the predictor of surgical complications in order to prevent them and improve this technique.
Fatigue and Dyspnoea as Main Persistent Post-COVID-19 Symptoms in Previously Hospitalized Patients: Related Functional Limitations and Disability
Authors: Fernández-de-las-Peñas César , Palacios-Ceña Domingo , Gómez-Mayordomo Víctor , Palacios-Ceña María , Rodríguez-Jiménez Jorge , de-la-Llave-Rincón Ana I. , Velasco-Arribas María , Fuensalida-Novo Stella , Ambite-Quesada Silvia , Guijarro Carlos , Cuadrado María L. , Florencio Lidiane L. , Arias-Navalón José A. , Ortega-Santiago Ricardo , Elvira-Martínez Carlos M. , Molina-Trigueros Luis J. , Torres-Macho Juan , Sebastián-Viana Tomas , Canto-Diez María Gabriela , Cigarán-Méndez Margarita , Hernández-Barrera Valentín , Arendt-Nielsen Lars
Published: September 2021

Background: Multicentre studies focussing on specific long-term post-COVID-19 symptoms are scarce. Objective: The aim of this study was to determine the levels of fatigue and dyspnoea, repercussions on daily life activities, and risk factors associated with fatigue or dyspnoea in COVID-19 survivors at long term after hospital discharge. Methods: Age, gender, height, weight, symptoms at hospitalization, pre-existing medical comorbidity, intensive care unit admission, and the presence of cardio-respiratory symptoms developed after severe acute respiratory syndrome coronavirus 2 infection were collected from patients who recovered from COVID-19 at 4 hospitals in Madrid (Spain) from March 1 to May 31, 2020 (first COVID-19 wave). The Functional Impairment Checklist was used for evaluating fatigue/dyspnoea levels and functional limitations. Results: A total of 1,142 patients (48% women, age: 61, standard deviation [SD]: 17 years) were assessed 7.0 months (SD 0.6) after hospitalization. Fatigue was present in 61% patients, dyspnoea with activity in 55%, and dyspnoea at rest in 23.5%. Only 355 (31.1%) patients did not exhibit fatigue and/or dyspnoea 7 months after hospitalization. Forty-five per cent reported functional limitations with daily living activities. Risk factors associated with fatigue and dyspnoea included female gender, number of pre-existing comorbidities, and number of symptoms at hospitalization. The number of days at hospital was a risk factor just for dyspnoea. Conclusions: Fatigue and/or dyspnoea were present in 70% of hospitalized COVID-19 survivors 7 months after discharge. In addition, 45% patients exhibited limitations on daily living activities. Being female, higher number of pre-existing medical comorbidities and number of symptoms at hospitalization were risk factors associated to fatigue/dyspnoea in COVID-19 survivors 7 months after hospitalization.
Myocardial Ischemia-Reperfusion Injury: Therapeutics from a Mitochondria-Centric Perspective
Authors: Zhou Manli , Yu Yunfeng , Luo Xiaoxin , Wang Jianzhang , Lan Xiaodong , Liu Pei , Feng Yu , Jian Weixiong
Published: September 2021

Coronary arterial disease is the most common cardiovascular disease. Myocardial ischemia-reperfusion injury caused by the initial interruption of organ blood flow and subsequent restoration of organ blood flow is an important clinical problem with various cardiac reperfusion strategies after acute myocardial infarction. Even though blood flow recovery is necessary for oxygen and nutrient supply, reperfusion causes pathological sequelae that lead to the aggravation of ischemic injury. At present, although it is known that injury will occur after reperfusion, clinical treatment always focuses on immediate recanalization. Mitochondrial fusion, fission, biogenesis, autophagy, and their intricate interaction constitute an effective mitochondrial quality control system. The mitochondrial quality control system plays an important role in maintaining cell homeostasis and cell survival. The removal of damaged, aging, and dysfunctional mitochondria is mediated by mitochondrial autophagy. With the help of appropriate changes in mitochondrial dynamics, new mitochondria are produced through mitochondrial biogenesis to meet the energy needs of cells. Mitochondrial dysfunction and the resulting oxidative stress have been associated with the pathogenesis of ischemia/reperfusion (I/R) injury, which play a crucial role in the pathophysiological process of myocardial injury. This review aimed at elucidating the mitochondrial quality control system and establishing the possibility of using mitochondria as a potential therapeutic target in the treatment of I/R injuries.
Tenofovir Is Superior to Entecavir on Tertiary Prevention for BCLC Stage 0/A Hepatocellular Carcinoma after Curative Resection
Authors: Tsai Ming-Chao , Wang Chih-Chi , Lee Wei-Chen , Lin Chih-Che , Chang Kuo-Chin , Chen Chien-Hung , Hung Chao-Hung , Lin Ming-Tsung , Hsiao Chang-Chun , Chen Chao-Long , Chien Rong-Nan , Hu Tsung-Hui
Published: September 2021

Background: It is unclear whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) have different effects on hepatocellular carcinoma (HCC) recurrence and death in patients receiving curative hepatectomy for hepatitis B virus (HBV)-related HCC. Aims: The aim of this study was to compare the long-term efficacy of ETV and TDF in HCC recurrence and overall survival (OS) of patients after curative hepatectomy. Methods: From January 2010 to December 2019, 20,572 patients with HCC who received hepatectomy were screened for study eligibility. Finally, a total of 219 consecutive patients treated with ETV (n = 146) or TDF (n = 73) after curative hepatectomy for HBV-related HCC of Barcelona Clinic Liver Cancer stage 0 or A were analyzed by propensity score matching (PSM) (2:1) analysis and competing risk analysis. HCC recurrence and OS of patients were compared between ETV and TDF groups. Result: After a median follow-up of 52.2 months, 81 patients (37.0%) had HCC recurrence, 33 (15.1%) died, and 5 (2.3%) received liver transplantation. TDF therapy was an independent protective factor for HCC recurrence compared with ETV therapy (HR, 1.687; 95% CI, 1.027–2.770, p = 0.039); however, no difference in the risk of death or liver transplantation. Results were similar in competing risk analysis. We further found that TDF therapy was significantly associated with a lower risk of late recurrence (HR, 4.705; 95% CI, 1.763–12.558, p = 0.002), but not in early recurrence. Conclusions: TDF therapy is associated with a significantly lower risk of HCC recurrence, especially of late recurrence, than ETV therapy among patients who undergo curative hepatectomy for HBV-related early-stage HCC.
Rituximab Treatment of Hairy Cell Leukemia in a Patient with Mycobacterium kansasii Infection: A Case Report
Authors: Mümmler Carlo , Zhang Danmei , Zimmermann Andreas , Mertsch Pontus , Fischer Luca , Greither Margarete , Khatamzas Elham , Ormanns Steffen , Heiß-Neumann Marion , Dreyling Martin , von Bergwelt-Baildon Michael , Boeck Stefan
Published: September 2021

Introduction: Infectious complications represent a major cause of morbidity and mortality in hairy cell leukemia (HCL) patients. Due to the immunosuppressive nature of the disease, these patients are frequently affected by opportunistic infections and rare pathogens. Furthermore, cytotoxic chemotherapy might lead to poor or even fatal outcomes in the setting of an active infection. Case Presentation: We report the case of a 62-year-old HCL patient who presented with recurrent fever episodes, pancytopenia, and mediastinal lymphadenopathy. A treatment decision against purine analogs and for rituximab mono was made as lymph node tissue revealed disseminated Mycobacterium kansasii infection. Together with specific antimycobacterial treatment, rituximab mono led to complete hematologic remission after 6 months without aggravating the accompanying infection. Conclusion: Here, we demonstrate successful treatment of HCL with rituximab in a patient with concomitant disseminated M. kansasii infection.
Making Industrial Policy Work for Decarbonization
Authors: Meckling Jonas
Published: September 2021

Industrial policy has begun to move into the center of debates on climate policy. This represents a shift away from climate policy as we know it—as classic environmental policy. Industrial policy and environmental policy differ in their policy goals, policy instruments, and distributional effects, one primarily concerned with economic development, the other with cutting greenhouse gas emissions. This raises questions about policy interactions between industrial and environmental policy in broader climate policy mixes and how these affect global decarbonization. This article identifies complementary and conflictual dynamics between industrial policy and environmental policy in both domestic and international climate politics. It shows how green industrial policy can advance climate goals and cooperation but can also present challenges to deepening climate cooperation and reducing greenhouse gas emissions. Developing an understanding of policy interactions is central to leveraging the potential of industrial policy to accelerate global decarbonization.
Dynamic Transitions between Neural States Are Associated with Flexible Task Switching during a Memory Task
Authors: Liu Wei , Kohn Nils , Fernández Guillén
Published: September 2021

Flexible behavior requires switching between different task conditions. It is known that such task switching is associated with costs in terms of slowed RT, reduced accuracy, or both. The neural correlates of task switching have usually been studied by requiring participants to switch between distinct task conditions that recruit different brain networks. Here, we investigated the transition of neural states underlying switching between two opposite memory-related processes (i.e., memory retrieval and memory suppression) in a memory task. We investigated 26 healthy participants who performed a think/no-think task while being in the fMRI scanner. Behaviorally, we show that it was more difficult for participants to suppress unwanted memories when a no-think was preceded by a think trial instead of another no-think trial. Neurally, we demonstrate that think–no-think switches were associated with an increase in control-related and a decrease in memory-related brain activity. Neural representations of task condition, assessed by decoding accuracy, were lower immediately after task switching compared with the nonswitch transitions, suggesting a switch-induced delay in the neural transition toward the required task condition. This suggestion is corroborated by an association between condition-specific representational strength and condition-specific performance in switch trials. Taken together, we provided neural evidence from the time-resolved decoding approach to support the notion that carryover of the previous task set activation is associated with the switching cost, leading to less successful memory suppression.
The Reading Signatures of Agreement Attraction
Authors: Lago Sol , Acuña Fariña Carlos , Meseguer Enrique
Published: September 2021

The comprehension of subject-verb agreement shows “attraction effects,” which reveal that number computations can be derailed by nouns that are grammatically unlicensed to control agreement with a verb. However, previous results are mixed regarding whether attraction affects the processing of grammatical and ungrammatical sentences alike. In a large-sample eye-tracking replication of Lago et al. (2015), we support this “grammaticality asymmetry” by showing that the reading profiles associated with attraction depend on sentence grammaticality. In ungrammatical sentences, attraction affected both fixation durations and regressive eye-movements at the critical disagreeing verb. Meanwhile, both grammatical and ungrammatical sentences showed effects of the attractor noun number prior to the verb, in the first- and second-pass reading of the subject phrase. This contrast suggests that attraction effects in comprehension have at least two different sources: the first reflects verb-triggered processes that operate mainly in ungrammatical sentences. The second source reflects difficulties in the encoding of the subject phrase, which disturb comprehension in both grammatical and ungrammatical sentences.
Extrapulmonary manifestations and complications of severe acute respiratory syndrome coronavirus-2 infection: a systematic review
Authors: Cho Jiacai , Lee Joanne , Sia Ching-Hui , Koo Chieh Sian , Tan Benjamin YQ , Hong Weizhen , Choi Ellie , Goh Xueying , Chai Louis , Chandran Nisha Suyien , Chua Horng Ruey , Chan Bernard PL , Muthiah Mark , Low Ting Ting , Yap Eng Soo , Lahiri Manjari
Published: September 2021

Introduction:

We aimed to describe the extrapulmonary manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, including their frequency, onset with respect to respiratory symptoms, pathogenesis and association with disease severity.

Methods:

We searched the MEDLINE and Embase databases for SARS-CoV-2-related studies. Meta-analysis, observational studies, case series and case reports published in English or Chinese between 1 January 2020 and 1 May 2020 were included. Reports with only paediatric or obstetric cases were excluded.

Results:

169 articles were included. Early manifestations (preceding respiratory symptoms until Day 6 of onset) included olfactory and gustatory disturbance (self-reported in up to 68% and 85% of cases, respectively), gastrointestinal symptoms (up to 65.9%) and rash (up to 20.4%). From Day 7 onwards, hypercytokinaemia, paralleled multi-organ complications including acute cardiac injury (pooled incidence of 17.7% in 1,412 patients, mostly with severe disease and 17.4% mortality), kidney and liver injury (up to 17% and 33%, respectively) and thrombocytopenia (up to 30%). Hypercoagulability resulted in venous thromboembolic events in up to 31% of all patients. Uncommon disease presentation and complications comprised Guillain-Barré syndrome, rhabdomyolysis, otitis media, meningoencephalitis and spontaneous pneumomediastinum.

Conclusion:

Although the systemic manifestations of SARS-CoV-2 infection are variegated, they are deeply interwoven by shared mechanisms. Two phases of extrapulmonary disease were identified: (a) an early phase with possible gastrointestinal, ocular and cutaneous involvement; and (b) a late phase characterised by multiorgan dysfunction and clinical deterioration. A clear, multidisciplinary consensus to define and approach thromboinflammation and cytokine release syndrome in SARS-CoV-2 is needed.
Patient-reported outcome measures and value-based medicine in paediatrics: a timely review
Authors: Tan Yi Hua , Siew Jia Xuan , Thomas Biju , Ng Kee Chong
Published: September 2021

Healthcare delivery is moving towards a more personalised and patient-centric approach. There is now an appropriate emphasis on providing value in our healthcare system. Patient-reported outcome measures (PROMs) assess our patients’ perceptions of the status of their health and quality of life, measured over a period of time. PROM is an integral component of a value-driven and value-based healthcare system and is key if we want to practise value-based medicine. In paediatrics and child health, PROMs, if implemented well with appropriate measurement tools that are regularly updated and validated in a self-learning healthcare ecosystem, will help to enhance personalised healthcare delivery and collectively improve the health of the community at large. This review covers the role of PROMs in paediatrics, as well as their role in value-based medicine.
Clinical audit of current Helicobacter pylori treatment outcomes in Singapore
Authors: Ang Tiing Leong , Lim Kim Wei , Ang Daphne , Wong Yu Jun , Tan Malcolm , Wong Andrew Siang Yih
Published: September 2021

Introduction:

H. pylori eradication reduces the risk of gastric malignancies and peptic ulcer disease. First-line therapies include 14-day PAC (proton pump inhibitor [PPI], amoxicillin, clarithromycin) and PBMT (PPI, bismuth, metronidazole, tetracycline). Second-line therapies include 14-day PBMT and PAL (PPI, amoxicillin, levofloxacin). This clinical audit examined current treatment outcomes in Singapore.

Methods:

Clinical data of H. pylori-positive patientswho underwent empirical first- and second-line eradication therapies from 1 January 2017 to 31 December 2018 were reviewed. Treatment success was determined by 13C urea breath test performed at least 4 weeks after treatment and 2 weeks off PPI.

Results:

A total of 963 patients (862 PAC, 36 PMC [PPI, metronidazole, clarithromycin], 18 PBMT, 13 PBAC [PAC with bismuth], 34 others) and 98 patients (62 PMBT, 15 PAL, 21 others) received first-and second-line therapies respectively. A 14-day treatment duration was appropriately prescribed for first- and second-line therapies in 65.2% and 82.7% of patients, respectively. First-line treatment success rates were noted for PAC (seven-day: 76.9%, ten-day: 88.3%, 14-day: 92.0%), PMC (seven-day: 0, ten-day: 75.0%, 14-day: 69.8%), PBMT (ten-day: 100%, 14-day: 87.5%) and PBAC (14-day: 100%). 14-day treatment was superior to seven-day treatment (90.8% vs. 71.4%; P = 0.028). PAC was superior to PMC (P < 0.001) but similar to PBMT (P = 0.518) and PBAC (P = 0.288) in 14-day therapies. 14-day second-line PAL and PBMT had similar efficacy (90.9% vs. 82.4%; P = 0.674).

Conclusion:

First-line empirical treatment using PAC, PBMT and PBAC for 14 days had similar efficacy. Success rates for second-line PBMT and PAL were similar.
Fucoidan-Coated Liposomes: A Target System to Deliver the Antimicrobial Drug Usnic Acid to Macrophages Infected with Mycobacterium tuberculosis
Authors: Lima Salviano Taciana , dos Santos Macedo Daniel Charles , de Siqueira Ferraz Carvalho Rafaela , Pereira Marcela Araújo , de Arruda Barbosa Vanessa Santos , dos Santos Aguiar Jaciana , Souto Fabrício Oliveira , Carvalho da Silva Maria da Paz , Lapa Montenegro Pimentel Lílian Maria , Correia de Sousa Luanna de Ângelis , Costa Silva Bezerra Sidicleia , da Silva Teresinha Gonçalves , da Silva Góes Alexandre José , Santos Magalhães Nereide Stela , Cajubá  de Britto Lira Nogueira Mariane
Published: September 2021

The present study describes the use of fucoidan, a negative sulfated polysaccharide, as a coating material for the development of liposomes targeted to macrophages infected with Mycobacterium tuberculosis. First, fucoidan was chemically modified to obtain a hydrophobized-fucoidan
derivative (cholesteryl-fucoidan) using a two-step microwave-assisted (μW) method. The total reaction time was decreased from 14 hours to 1 hour while maintaining the overall yield. Cholesterylfucoidan was then used to prepare surface-modified liposomes containing usnic acid (UA-LipoFuc),
an antimicrobial lichen derivative. UA-LipoFuc was evaluated for mean particle size, polydispersity index (PDI), surface charge (ζ), and UA encapsulation efficiency. In addition, a cytotoxicity study, competition assay and an evaluation of antimycobacterial activity against macrophages
infected with M. tuberculosis (H37Ra) were performed. When the amount of fucoidan was increased (from 5 to 20 mg), vesicle size increased (from 168 ± 2.82 nm to 1.18 ± 0.01 μm). Changes in from +20 ± 0.41 mV for uncoated liposomes to −5.41 ± 0.23
mV for UA-LipoFuc suggested that the fucoidan was placed on the surface of the liposomes. UA-LipoFuc exhibited a lower IC50 (8.26 ± 1.11 μM) than uncoated liposomes (18.37 ± 3.34 μM), probably due to its higher uptake. UA-LipoFuc5 was internalized
through the C-type carbohydrate recognition domain of the cell membrane. Finally, usnic acid, both in its free form and encapsulated in fucoidan-coated liposomes (UA-LipoFuc5), was effective against infected macrophages. Hence, this preliminary investigation suggests that encapsulated
usnic acid will aid in further studies related to infected macrophages and may be a potential option for tuberculosis treatment.
Multiscale interactions between monsoon intra-seasonal oscillations and low pressure systems that produce heavy rainfall events of different spatial extents
Authors: Nikumbh Akshaya C , Chakraborty Arindam , Bhat G.S. , Frierson Dargan M. W.
Published: September 2021

The sub-seasonal and synoptic-scale variability of the Indian summer monsoon rainfall are controlled primarily by monsoon intra-seasonal oscillations (MISO) and low pressure systems (LPS), respectively. The positive and negative phases of MISO lead to alternate epochs of above-normal (active) and below-normal (break) spells of rainfall. LPSs are embedded within the different phases of MISO and are known to produce heavy precipitation events over central India. Whether the interaction with the MISO phases modulates the precipitation response of LPSs, and thereby the characteristics of extreme rainfall events (EREs) remains unaddressed in the available literature. In this study, we analyze the LPSs that produce EREs of various spatial extents viz., Small, Medium, and Large over central India from 1979 to 2012. We also compare them with the LPSs that pass through central India and do not give any ERE (LPS-noex). We find that thermodynamic characteristics of LPSs that trigger different spatial extents of EREs are similar. However, they show differences in their dynamic characteristics. The ERE producing LPSs are slower, moister and more intense than LPS-noex. The LPSs that lead to Medium and Large EREs tend to occur during the positive phase of MISO when an active monsoon trough is present over central India. On the other hand, LPS-noex and the LPSs that trigger Small EREs occur mainly during the neutral or negative phases of the MISO. The large-scale dynamic forcing, intensification of LPSs, and diabatic generation of low-level potential vorticity due to the presence of active monsoon trough help in the organization of convection and lead to Medium and Large EREs. On the other hand, the LPSs that form during the negative or neutral phases of MISO do not intensify much during their lifetime and trigger scattered convection, leading to EREs of small size.
The Effect of Latent and Error Non-Normality on Measures of Fit in Structural Equation Modeling
Authors: Jobst Lisa J. , Auerswald Max , Moshagen Morten
Published: September 2021

Prior studies investigating the effects of non-normality in structural equation modeling typically induced non-normality in the indicator variables. This procedure neglects the factor analytic structure of the data, which is defined as the sum of latent variables and errors, so it is unclear whether previous results hold if the source of non-normality is considered. We conducted a Monte Carlo simulation manipulating the underlying multivariate distribution to assess the effect of the source of non-normality (latent, error, and marginal conditions with either multivariate normal or non-normal marginal distributions) on different measures of fit (empirical rejection rates for the likelihood-ratio model test statistic, the root mean square error of approximation, the standardized root mean square residual, and the comparative fit index). We considered different estimation methods (maximum likelihood, generalized least squares, and (un)modified asymptotically distribution-free), sample sizes, and the extent of non-normality in correctly specified and misspecified models to investigate their performance. The results show that all measures of fit were affected by the source of non-normality but with varying patterns for the analyzed estimation methods.
Need for and Receipt of Substance Use Disorder Treatment Among Adults, by Gender, in the United States
Authors: Martin Caitlin E. , Parlier-Ahmad Anna Beth , Beck Lori , Scialli Anna , Terplan Mishka
Published: September 2021

Objectives

Disparities in substance use disorder (SUD) treatment use persist across groups, including gender. Using a gender-informed approach to expand treatment capacity and reduce barriers to treatment engagement is vital. We examined SUD treatment need and receipt among people with SUD in the United States, by gender, and assessed gender-specific sociodemographic factors associated with unmet need for SUD treatment and reported treatment barriers.

Methods

We conducted an analysis of data among adults aged ≥18 with a past-year SUD from the National Survey on Drug Use and Health (2015-2018). We computed population-adjusted frequencies and proportions for SUD treatment need and receipt and assessed gender differences. Multivariate logistic regression assessed gender-specific sociodemographic variables associated with SUD treatment receipt.

Results

Among adults with a past-year SUD, 63.4% were men and 36.6% were women ( P < .001), only 10.6% received SUD treatment, and a greater percentage of women than men needed treatment for opioid use disorder (11.9% vs 9.9%; P = .002). Receipt of SUD treatment was lowest among women with alcohol use disorder followed by men with alcohol use disorder (7.5% vs 8.9%; P = .052). Non-Latinx Black men had fewer than half the adjusted odds of receiving SUD treatment than non-Latinx White men (adjusted odds ratio [aOR] = 0.44; 95% CI, 0.27-0.71). Latinx women (aOR = 0.37; 95% CI, 0.18-0.73) and non-Latinx Black women (aOR = 0.51; 95% CI, 0.27-0.94) had significantly lower odds of receiving SUD treatment than non-Latinx White women.

Conclusions

As public health efforts target expanding SUD treatment capacity and addressing disparities in use of SUD treatment, interventions informed by gender and culture should be prioritized.
Ambiguous Signaling in Regulatory Conversations How Miscommunication and Hierarchy Hamper Voluntary Regulatee Cooperation
Authors: Kasdorp Aute , Schakel Leonie
Published: September 2021

This case study investigates interactions between inspectors and regulatee representatives during regulatory conversations. We study how health care inspectors pursue voluntary cooperation from internal supervisors of health care providers to alter organizational management practices. We identify ambiguity as a central characteristic of the regulatory conversations. We observe several discrepancies as inspectors display hierarchical behavior incongruent with the horizontal relationship they aim for—and incongruent with the relationship style that internal supervisors expect. Analyzing these discrepancies in terms of relationship types and associated relational signals helps explain and prevent suboptimal communication and reduced acceptance of regulators’ demands by regulatees.
Heat Extraction Performance and Optimization for a Doublet-well Geothermal System in Dezhou, China
Authors: Xu Tianfu , Zhao Yue’an , Zhao Jichu , Zhang Lanxin , Liu Shuai , Liu Zhitao , Feng Bo , Feng Guanhong , Yue Gaofan
Published: September 2021

Dezhou City is located in northwestern Shandong Province, China, and is rich in geothermal resources. Approximately 30% of the geothermal wells and geothermal heating areas of Shandong Province are located in Dezhou. A doublet-well layout geothermal system was completed by the Lubei Geo-engineering Exploration Institute for local winter heating, which has been in operation for 4 years. The wellbores penetrated the Guantao Formation with a well spacing of 180 m. This study aims to assess the heat extraction performance of the current well layout and predict the temperature evolution and lifespan. Furthermore, larger well spacing schemes were used in a simulation to test the heat supply potential and sustainability. In this study, the thermal conductivity and permeability were calibrated using in situ measured data from a field production test. A relatively high permeability layer was found between the depths of 1468 and 1536 m. The temperature remained stable in the first 6 years and then started to decrease. The recharging (injection) water tended to concentrate along the bottom highly permeable layer and accounted for over 64% of the outflow in the 100th year of the simulation test. The outflow temperature decreased from 53.9°C to 50°C in the 32nd year, making it less viable for subsequent sustainable exploitation. Hence, a larger well spacing is required for long-term operation based on the same geothermal reservoir. It was found that a spacing of 400 m could guarantee an outflow temperature above 50°C over a 100-year lifespan with an 80 m3/h pumping (production) rate. Moreover, the sustainability of the 600-m spacing was almost 2.5 times that of the 400 m case. The modeling and analysis method can be useful for the development and optimization of a doublet-well geothermal system under similar conditions.
Outcomes of an Ear Camp Conducted in Bhutan by Thai Rural ENT Foundation—A Descriptive Study
Authors: Pradhan Umesh , Chindavijak Somjin , Tanamai Napas
Published: September 2021

Background:

The Thai Rural ENT foundation has been conducting ear camps in Bhutan for many years to address the shortage of ENT specialists in the kingdom where patients are examined and treated for various ear illnesses. However, there has been no study conducted to assess the outcomes of such camps. This is the first study of its kind to be carried out in Bhutan.

Objective:

To study the spectrum of ear cases seen during the mobile ear camp, the intervention done and treatment outcomes.

Materials and Methods:

The study enrolled patients with ear disorders who presented to the mobile ear camp at Monggar Regional Referral Hospital, Bhutan, from January 6, 2020, to January 8, 2020. The following data were recorded: demographic details, preoperative clinical symptoms and otoscopic findings, preoperative audiogram, treatment or surgery done, postoperative middle ear and mastoid infection, wound infection, graft condition, any complications, and postoperative audiogram of operated cases. Patients who underwent surgery were followed up at 1 day, 6 weeks, and 2 months postoperatively.

Results:

Two hundred ten patients presented with otologic conditions and 43 underwent surgeries. Otitis media was the commonest disease detected, and tympanoplasty was the commonest surgery performed. The tympanic membrane closure rate was 92.1%, and the rate of hearing improvement was 63.2%.

Conclusion:

The ear camp had beneficial effect and showed good results.
Technology, Sexual Violence, and Power-Evasive Politics: Mapping the Anti-violence Sociotechnical Imaginary
Authors: Shelby Renee
Published: September 2021

Recent discussions on technology and gender-violence prevention emphasize that technoscientific applications often advance pro-punishment logics that enact gendered inequalities. Less attention has focused on racialized dimensions and how technology might advance abolitionist and transformative justice agendas. In response, this article considers how inventors mobilize technology as a frontline response to sexual violence, in which technoscience—rather than police—enables individuals, friends, and family to provide safety and mutual aid. Through analysis of seven popular technologies produced between 2010 and 2020, this paper documents how their “abolitionist sensibility” is accompanied by fellow-traveler discourses that are unattuned to intersecting power relations. Findings suggest that while this sociotechnical imaginary is reacting to state power, it reinforces a race-neutral and techno-optimistic vision for building a violence-free future. These power-evasive politics may thus signal increased susceptibility to carceral creep and coercive surveillant regimes. After discussing these double-edge politics, I conclude by discussing power formations that are left unexamined in the imaginary and how to cultivate a counter-carceral praxis in line with transformative justice goals.
Cognitive Impairment and Delirium in Older Patients Undergoing Major Head and Neck Surgery
Authors: Goldstein David P. , Blasco Michael , de Almeida John , Su Jie , Xu Wei , Cohen Marc , Sklar Michael , Alibhai Shabbir
Published: September 2021

The study objective was to measure the prevalence and predictors of cognitive impairment (CI) and delirium. Adults undergoing major head and neck cancer surgery completed the Clock Draw Test to screen for CI, defined as a score of 0 or 1. Postoperative delirium was recorded. Predictors of delirium and length of stay were assessed by univariate logistic regression and the latter with multivariate linear regression. Overall 274 patients were included, of which 47% had a Clock Draw Test score of 0 or 1. Post‐operative delirium occurred in 17 (6%). CI was a predictor of postoperative delirium (odds ratio, 3.9; 95% CI, 1.2‐12; P =. 02). Postoperative delirium was a predictor of increased length of stay (adjusted odds ratio, 1.30; 95% CI, 1.07‐1.57; P =. 0073) on multivariate regression while baseline Clock Draw Test result was not a predictor on univariate regression (P =. 98). Screening for CI can help predict delirium and facilitate targeted interventions in the postoperative period.
Peripheral Auditory Function in Young HIV‐Positive Adults With Clinically Normal Hearing
Authors: Niemczak Christopher E. , White‐Schwoch Travis , Fellows Abigail , Magohe Albert , Gui Jiang , Rieke Catherine , Nicol Trent , Massawe Enica R. , Moshi Ndeserua , Kraus Nina , Buckey Jay C.
Published: September 2021

Objective

Little is known about peripheral auditory function in young adults with HIV, who might be expected to show early evidence of hearing loss if HIV infection or treatment does affect peripheral function. The goal of this study was to compare peripheral auditory function in 2 age‐ and gender‐matched groups of young adults with clinically normal hearing with and without HIV.

Study Design

Matched cohort study with repeated measures.

Setting

Infectious disease center in Dar es Salaam, Tanzania.

Methods

Participants included HIV‐positive (n = 38) and HIV‐negative (n = 38) adults aged 20 to 30 years who had clinically normal hearing, defined as type A tympanograms, air conduction thresholds ≤25 dB HL bilaterally from 0.5 to 8 kHz, and distortion product otoacoustic emissions (DPOAEs) >6 dB above the noise floor bilaterally from 1.5 to 8 kHz. Participants were tested multiple times over 6‐month intervals (average, 2.7 sessions/participant) for a total of 208 observations. Primary outcome measures included tympanograms, air conduction audiograms, DPOAEs, and click‐evoked auditory brainstem responses.

Results

HIV groups did not significantly differ in age, static immittance, or air conduction thresholds. HIV‐positive status was independently associated with approximately 3.7‐dB lower DPOAE amplitudes from 2 to 8 kHz (95% CI, 1.01‐6.82) in both ears and 0.04‐µV lower (95% CI, 0.003‐0.076) auditory brainstem response wave I amplitudes in the right ear.

Conclusion

Young adults living with HIV have slightly but reliably smaller DPOAEs and auditory brainstem response wave I amplitudes than matched HIV‐negative controls. The magnitude of these differences is small, but these results support measuring peripheral auditory function in HIV‐positive individuals as they age.
How Do Academic Otolaryngologists Decide to Implement New Procedures Into Practice?
Authors: Powers Bethany , Smith Cara Damico , Arroyo Natalia , Francis David O. , Fernandes‐Taylor Sara
Published: September 2021

Objective

To identify barriers and facilitators to adoption of a new surgical procedure via an implementation science framework to characterize associated socioemotional, clinical, and decision‐making processes.

Study Design

Qualitative study with a semistructured interview approach.

Setting

Large tertiary care referral center.

Methods

Academic otolaryngologists with at least 2 years of practice were identified and interviewed. Transcripts were thematically coded and separated into steps in the clinical pathway. Synthesis of major themes characterized facilitators and barriers to uptake of a new surgical technique.

Results

Of 22 otolaryngologists, 19 were interviewed (85% male). They had a median 18 years of practice (interquartile range, 7.8‐26.3), and 65% were subspecialty trained. In the decision to implement a new procedure, improving patient outcomes and addressing unmet clinical needs facilitated adoption, whereas costs and adopting profit‐driven technologies without improved outcomes were barriers. In patient consults, establishing trust facilitated implementation of new techniques; barriers included participants’ hesitation to communicate about the unknowns of a new procedure. Intraoperatively, little change to existing workflow or improved efficiency facilitated adoption, while a substantial learning curve for the new procedure was a barrier. Achieving favorable outcomes and patient satisfaction sustained implementation of new procedures. Too few referrals or indications for the new procedure hindered implementation.

Conclusion

Our study demonstrates that innovation in otolaryngology is often an individual iterative process that providers pursue to improve patients’ outcomes. Although models for the oversight of surgical innovation emphasize the need for evidence, obtaining sufficient numbers of providers and patients to generate evidence remains a challenge in specialty surgical practice.
Approach to Management of Wandering in Dementia: Ethical and Legal Issue
Authors: Agrawal Adesh Kumar , Gowda Mahesh , Achary Umesh , Gowda Guru S. , Harbishettar Vijaykumar
Published: September 2021

Wandering behavior is one of the most important and challenging management aspects in persons with dementia. Wandering behavior in people with dementia (PwD) is associated with an increased risk of falls, injuries, and fractures, as well as going missing or being lost from a facility. This causes increased distress in caregivers at home and in healthcare facilities. The approach to the comprehensive evaluation of the risk assessment, prevention, and treatment needs more strengthening and effective measures as the prevalence of wandering remains high in the community. Both the caregiver and clinicians need a clear understanding and responsibility of ethical and legal issues while managing and restraining the PwD. Ethical and legal issues especially in the light of the new Indian Mental Healthcare Act of 2017, related to confinement by family members in their homes by family caregivers, seclusion, physical or chemical restraints, other pharmacological and behavioral treatment, highlighting their effectiveness as well as adverse consequences are discussed. This article attempts to address an approach in managing wandering behavior in PwD in light of MHCA, 2017