bluuebunny/crossref_metadata_2025 huggingface dataset:
Counterterrorism, sanctions and financial access challenges: Course corrections to safeguard humanitarian action
Authors: Eckert Sue E.
Published: February 2022

This article provides an overview of the impact of United Nations (UN) sanctions and counterterrorism (CT) measures on humanitarian action. The mandatory requirements of UN Security Council Resolutions 1267 and 1373 on member States to prohibit the provision of “funds, financial assets or economic resources” to terrorists complicates the work of humanitarian actors delivering assistance in areas where groups designated under the 1267 regime control territory. After explaining the impact of sanctions and CT measures on humanitarian actors, the article explores three primary sets of challenges encountered by such actors: (1) lack of clarity and adequate legal protection for carrying out humanitarian activities in countries subject to sanctions or areas in which designated entities operate; (2) financial access difficulties or de-risking by financial institutions limiting the ability of non-profit organizations (NPOs) to transfer funds to higher-risk jurisdictions due to banks’ risk aversion or fear of regulatory scrutiny of such transactions; and (3) conditions placed in funding contracts by donors effectively offloading CT and sanctions risks onto beneficiaries. The article analyzes experience with UN humanitarian carve-outs (exceptions as employed in the Somalia sanctions regime and case-by-case exemptions utilized in the North Korea regime), explaining why exceptions are the optimal solution for humanitarian actors. New data are presented indicating that the scope and scale of financial access difficulties experienced by NPOs have grown. Financial institutions, concerned about regulatory requirements to counter terrorism financing, are increasingly reluctant to provide banking services to NPOs working in highly sanctioned jurisdictions, and the resulting de-risking by banks results in significant problems for humanitarian organizations needing to move funds abroad. Additionally, contractual conditions related to CT and sanctions compliance are routinely employed by donors, resulting in an offloading of risk onto recipients without appropriate clarity and guidance from donors. Numerous initiatives in recent years have called attention to the challenges that humanitarians face: stakeholder dialogues, high-level meetings and other discussion fora promote broader understanding among participants and acknowledgement of the impacts that these polices have on humanitarian action. UN action to renew the 1267 regime's mandate and the consideration of a humanitarian carve-out in Afghanistan in the aftermath of the Taliban's takeover represent opportunities to reform sanctions in order to better protect humanitarian action. Recommendations are presented for each of the three sets of challenges, with an urgent call for the Security Council to embrace the opportunity for reform and more effectively balance the equally critical objectives of countering terrorism and safeguarding humanitarian action.
Development and Assessment of an ALLSSA‐Based Atmospheric Weighted Mean Temperature Model With High Time Resolution for GNSS Precipitable Water Retrieval
Authors: Ma Yongchao , Chen Peng , Liu Tong , Xu Guochang , Lu Zhiping
Published: January 2022

The atmosphere weighted mean temperature, Tm, is an essential parameter for retrieving precipitable water from the ground‐based Global Navigation Satellite Systems (GNSS). The accuracy of high temporal resolution GNSS precipitable water vapor (PWV) estimation requires wideband Tm information and its magnitude. However, existing Tm empirical models use trigonometric functions with only fixed amplitude and low‐frequency for time fitting, which limits real‐time or near real‐time PWV retrieval from GNSS observation. Thus, an improved Tm model for China, LTCm, containing more frequency information of Tm, based on the antileakage least‐squares spectrum analysis by utilizing the ERA5 pressure‐level products during the years 2015–2019, is developed. Both Tm data from ERA5 pressure‐level products and radiosonde stations distributed in China over 2020 are selected as reference values to verify the performance of the LCTm model. The results show that the LCTm model yields significant performance against other models in Tm estimation over China, especially in marine regions and high‐altitude areas. Furthermore, the LCTm model can generally achieve a mean Bias/root mean square (RMS) of −0.33 K/2.06 K in contrast to ERA5 pressure‐level products and 0.03 K/3.47 K in comparison with radiosonde, which corresponds to a 7.2%–13.8% improvement against GPT2w, GTm‐III, and Bevis. Moreover, LCTm has σ

pwv
and σ

pwv
/PWV values of 0.27 mm and 1.25% when used to retrieve GNSS‐PWV, respectively. Consequently, the LCTm model that considers high‐frequency information of Tm can obtain more reliable Tm values. Therefore, the LCTm model can be applied to real‐time or near real‐time GNSS PWV retrieval, which is of great significance for GNSS meteorological research.
Polarization Properties of 3‐D Field Line Resonances
Authors: Elsden T. , Wright A. N.
Published: February 2022

Recent work has shown that field line resonances (FLRs) can form with intermediate magnetic field polarizations, that is, between toroidal (azimuthal) and poloidal (radial). In this case, they are referred to as “3‐D”, given that the equilibrium and therefore associated wave solutions vary in all three dimensions. Such 3‐D variations in the medium can be expected in the magnetosphere in particular during the presence of a plasmaspheric drainage plume in the dusk flank. In this case, strong field‐aligned currents driven by FLRs can form along contours of Alfvén frequency which are very asymmetric azimuthally. In this study, we use magnetohydrodynamic (MHD) simulations performed in a background dipole magnetic field, to consider what the satellite signatures would be for a spacecraft observing such non‐toroidal FLRs under different magnetopause driving conditions. We consider how the 3‐D nature impacts the amplitude and phase relations traditionally expected for FLRs. We find that in the 3‐D FLR regions of intermediate polarization, the FLR has strong contributions from both the radial and azimuthal field components (velocity, magnetic or electric) and these are in or out of phase. We show how hodograms can be used to infer the FLR polarization in these cases as well as provide predictions for the variation of the FLR polarization with MLT across a plasmaspheric plume. We further show how the presence of a significant global fast mode can skew the resulting polarization estimates.
Long‐Runout‐Landslide‐Induced Debris Flow: The Role of Fine Sediment Deposition Processes in Debris Flow Propagation
Authors: Nishiguchi Yuki , Uchida Taro
Published: January 2022

Landslide‐induced debris flows can travel long distances. Many field studies, laboratory experiments, and theoretical studies have been conducted to clarify the mechanisms of long‐runout landslides. However, information concerning landslide‐induced debris flows is still inadequate despite several explanations proposed. Thus, we collected various forms of data, including video images and light detection and ranging data, for a landslide‐induced debris flow that occurred on 28 July 2015, in Fukaminato River, Japan, and clarified the debris flow behavior from initiation to deposition. We showed that the water content of the debris flow should only be approximately 30% immediately after landslides occurred at the site. However, a fluid phase‐dominated flow flowed over 1.2 km, expanding the damaged area. We inferred that the fine sediments behaved as part of the interstitial fluid in the debris flow and that, during debris flow deposition, some fine sediments were stored in the interstitial space of the riverbed and did not contribute to forming the skeleton of deposits. We conducted a numerical simulation to test the processes of fluid phase‐dominated flow propagation, focusing on the flow and deposition of fine sediments. Our simulation results suggest that fine sediments' flow and depositional processes significantly influence both the initiation of fluid phase‐dominated debris flow and the travel distance of landslide‐induced debris flow.
Quantifying the Uncertainty Created by Non‐Transferable Model Calibrations Across Climate and Land Cover Scenarios: A Case Study With SWMM
Authors: Sytsma Anneliese , Crompton Octavia , Panos Chelsea , Thompson Sally , Mathias Kondolf G.
Published: February 2022

Predictions of urban runoff are heavily reliant on semi‐distributed models, which simulate runoff at subcatchment scales. These models often use “effective” model parameters that average across the small‐scale heterogeneity. Here we quantify the error in model prediction that arises when the optimal calibrated value of effective parameters changes with model forcing. The uncertainty this produces, which we refer to as “calibration parameter transfer uncertainty,” can undermine the usefulness of important applications of urban hydrologic models, for example, to predict the hydrologic response to novel climate or development scenarios. Using the urban hydrologic model SWMM (“Stormwater Management Model”) as a case study, we quantify the transferability of two calibrated effective parameters: subcatchment “width” and “connected impervious area.” Through numerical experiments, we simulate overland flow across a highly simplified synthetic urban landscape subject to a range of scenarios (combinations of storm events, soil types, and impervious areas). For each scenario, we calibrate SWMM “width” and “connected impervious area” parameters to the outcomes of a distributed model. We find that the calibrated values of these parameters vary with soil, storm, and land cover forcing. This variation across forcing parameters can result in prediction errors up to a magnitude of 60% when a calibrated SWMM is used to predict runoff following changes in climate and land cover. Such calibration transfer uncertainty is largely unaccounted for in urban hydrologic modeling. These results point to a need for additional research to determine how to use urban hydrologic models to make robust predictions across future conditions.
Effect of early granulocyte-colony-stimulating factor administration in the prevention of febrile neutropenia and impact on toxicity and efficacy of anti-CD19 CAR-T in patients with relapsed/refractory B-cell lymphoma
Authors: Liévin Raphaël , Di Blasi Roberta , Morin Florence , Galli Eugenio , Allain Vincent , De Jorna Romain , Vercellino Laetitia , Parquet Nathalie , Mebarki Miryam , Larghero Jerome , de Kerviler Eric , Madelaine Isabelle , Caillat-Zucman Sophie , Chevret Sylvie , Thieblemont Catherine
Published: January 2022

Chimeric Antigen Receptor T cells (CAR-T) are an outbreaking treatment option for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are the most common specific toxicities, while severe neutropenia and infections are often observed as well. From March 2020, early G-CSF prophylaxis at day (D) two post-infusion was systematically proposed. We then compared patients treated before that date who did not receive G-CSF or who received late (after D5) G-CSF as control group. Patients administered with early G-CSF had similar duration of grade 4 neutropenia but significantly decreased incidence of febrile neutropenia (58% versus 81%, p = 0.018). Similar rate of toxicities was observed, including overall and grade 3-4 CRS (p = 0.93 and p = 0.28, respectively), and overall and grade 3-4 ICANS (p = 0.62 and p = 0.88, respectively). We observed no difference in the quality of CAR T-cells expansion (p = 0.79, %Cmax), nor in response rate (best ORR, 57.6% vs 61.8%, p = 0.93), nor survival even in a group of patients adjusted by a propensity score. In conclusion, early G-CSF administration was safe and effective in reducing febrile neutropenia without impact on toxicities nor on anti-lymphoma activity of CAR-T.
Molecular insights into the interaction of HPV-16 E6 variants against MAGI-1 PDZ1 domain
Authors: Araujo-Arcos Lilian Esmeralda , Montaño Sarita , Bello-Rios Ciresthel , Garibay-Cerdenares Olga Lilia , Leyva-Vázquez Marco Antonio , Illades-Aguiar Berenice
Published: February 2022

Oncogenic protein E6 from Human Papilloma Virus 16 (HPV-16) mediates the degradation of Membrane-associated guanylate kinase with inverted domain structure-1 (MAGI-1), throughout the interaction of its protein binding motif (PBM) with the Discs-large homologous regions 1 (PDZ1) domain of MAG1-1. Generic variation in the E6 gene that translates to changes in the protein’s amino acidic sequence modifies the interaction of E6 with the cellular protein MAGI-1. MAGI-1 is a scaffolding protein found at tight junctions of epithelial cells, where it interacts with a variety of proteins regulating signaling pathways. MAGI-1 is a multidomain protein containing two WW (rsp-domain-9), one guanylate kinase-like, and six PDZ domains. PDZ domains played an important role in the function of MAGI-1 and served as targets for several viral proteins including the HPV-16 E6. The aim of this work was to evaluate, with an in silico approach, employing molecular dynamics simulation and protein–protein docking, the interaction of the intragenic variants E-G350 (L83V), E-C188/G350 (E29Q/L83V), E-A176/G350 (D25N/L83V), E6-AAa (Q14H/H78Y/83V) y E6-AAc (Q14H/I27RH78Y/L83V) and E6-reference of HPV-16 with MAGI-1. We found that variants E-G350, E-C188/G350, E-A176/G350, AAa and AAc increase their affinity to our two models of MAGI-1 compared to E6-reference.
Tailored up-conversion luminescence output of Al-modulated KYbF4: Er3+ nanocrystals for a low-temperature sensor
Authors: Cui Zhenzhen , Zhao Lei , Wang Ting , Cao Jiangyan , Qiao Yufang , Pi Chaojie , Fang Zhaohui , Qiu Jianbei , Xu Xuhui , Yu Xue
Published: January 2022

Tailored up-conversion luminescence output of Al-modulated KYbF4: Er3+ nanocrystals for a low-temperature sensor.
Theoretical exploration of diverse electron-deficient core and terminal groups in A–DA′D–A type non-fullerene acceptors for organic solar cells
Authors: Shao Yueyue , Lu Tian , Li Minjie , Lu Wencong
Published: January 2022

The influences triggered by the structurally diverse electron-withdrawing terminal group and fuse-ring electron-deficient core on the performance of NFAs OSCs are comprehensively investigated by using DFT, TD-DFT and Marcus charge transfer theory.
Design and synthesis of amino acid derivatives of substituted benzimidazoles and pyrazoles as Sirt1 inhibitors
Authors: Purushotham Nikil , Singh Mrityunjay , Paramesha Bugga , Kumar Vasantha , Wakode Sharad , Banerjee Sanjay K. , Poojary Boja , Asthana Shailendra
Published: January 2022

Owing to its presence in several biological processes, Sirt1 acts as a potential therapeutic target for many diseases.
High-yield one-pot synthesis of polyrotaxanes with tunable well-defined threading ratios over a wide range
Authors: Noritomi Takako , Jiang Lan , Yokoyama Hideaki , Mayumi Koichi , Ito Kohzo
Published: January 2022

In this work, we report a high-yield one-pot synthesis of polyrotaxane (PR), composed of (2-hydroxypropyl)-α-cyclodextrin (hpCD) and polyethylene glycol (PEG), with well-defined hpCD threading ratios controllable across a wide range from 0.64% to 10%.
Comorbidities in Children with COVID-19 and MIS-C/PIMS-TS and
Risk Factors for Hospitalization, Severe Disease, Intensive Care and
Death
Authors: Ankermann Tobias , Brinkmann Folke
Published: February 2022

This narrative review sums up data from the SARS-CoV-2-pandemia on preexisting
disease/underlying conditions/comorbidities and risk factors in
children for severe COVID-19 and MIS-C/PIMS-TS as well as
hospitalization and mortality. Young infants and adolescents are at highest risk
of hospital and PICU admission. Two or more comorbidities rather than single
entities pose a risk for more severe courses of SARS-CoV-2 infection in
children. Asthma and malignancy do not increase complication rates.
MIS-C/PIMS-TS is not associated with any specific underlying
disease.
Can Prehospital Data Improve Early Identification of Sepsis in Emergency Department? An Integrative Review of Machine Learning Approaches
Authors: Desai Manushi D. , Tootooni Mohammad S. , Bobay Kathleen L.
Published: February 2022

Background Sepsis is associated with high mortality, especially during the novel coronavirus disease 2019 (COVID-19) pandemic. Along with high monetary health care costs for sepsis treatment, there is a lasting impact on lives of sepsis survivors and their caregivers. Early identification is necessary to reduce the negative impact of sepsis and to improve patient outcomes. Prehospital data are among the earliest information collected by health care systems. Using these untapped sources of data in machine learning (ML)-based approaches can identify patients with sepsis earlier in emergency department (ED).

Objectives This integrative literature review aims to discuss the importance of utilizing prehospital data elements in ED, summarize their current use in developing ML-based prediction models, and specifically identify those data elements that can potentially contribute to early identification of sepsis in ED when used in ML-based approaches.

Method Literature search strategy includes following two separate searches: (1) use of prehospital data in ML models in ED; and (2) ML models that are developed specifically to predict/detect sepsis in ED. In total, 24 articles are used in this review.

Results A summary of prehospital data used to identify time-sensitive conditions earlier in ED is provided. Literature related to use of ML models for early identification of sepsis in ED is limited and no studies were found related to ML models using prehospital data in prediction/early identification of sepsis in ED. Among those using ED data, ML models outperform traditional statistical models. In addition, the use of the free-text elements and natural language processing (NLP) methods could result in better prediction of sepsis in ED.

Conclusion This study reviews the use of prehospital data in early decision-making in ED and suggests that researchers utilize such data elements for prediction/early identification of sepsis in ML-based approaches.
Evolution of nuclear charge radii in copper and indium isotopes *
Authors: An Rong , Jiang Xiang , Cao Li-Gang , Zhang Feng-Shou
Published: January 2022

Systematic trends in nuclear charge radii are of great interest due to universal shell effects and odd-even staggering (OES). The modified root mean square (rms) charge radius formula, which phenomenologically accounts for the formation of neutron-proton (np) correlations, is here applied for the first time to the study of odd-Z copper and indium isotopes. Theoretical results obtained by the relativistic mean field (RMF) model with NL3, PK1 and NL3* parameter sets are compared with experimental data. Our results show that both OES and the abrupt changes across

and 82 shell closures are clearly reproduced in nuclear charge radii. The inverted parabolic-like behaviors of rms charge radii can also be described remarkably well between two neutron magic numbers, namely

to 50 for copper isotopes and

to 82 for indium isotopes. This implies that the np-correlations play an indispensable role in quantitatively determining the fine structures of nuclear charge radii along odd-Z isotopic chains. Also, our conclusions have almost no dependence on the effective forces.
Effects of Self-gravity on Mass-loss of the Post-impact Super-Earths
Authors: Huang Jiang , Zhong Wei , Yu Cong
Published: January 2022

Kepler’s observations show most of the exoplanets are super-Earths. The formation of a super-Earth is generally related to the atmospheric mass loss that is crucial in the planetary structure and evolution. The shock driven by the giant impact will heat the planet, resulting in the atmosphere escape. We focus on whether self-gravity changes the efficiency of mass loss. Without self-gravity, if the impactor mass is comparable to the envelope mass, there is a significant mass-loss. The radiative-convective boundary will shift inward by self-gravity. As the temperature and envelope mass increase, the situation becomes more prominent, resulting in a heavier envelope. Therefore, the impactor mass will increase to motivate the significant mass loss, as the self-gravity is included. With the increase of envelope mass, the self-gravity is particularly important.
Explaining the Multiwavelength Emission of Hard-TeV BL Lac Objects Using a Truncated Conical Jet Model
Authors: Lei Maichang , Zheng Yuan , Zhang Jianfu , Wang Jiancheng
Published: January 2022

Hard-TeV BL Lac objects are newly identified populations of active galactic nuclei with the emitted γ-ray photons well above TeV energies. In this paper, we explain the multiwavelength emission of six Hard-TeV BL Lac objects by using a truncated conical emission region of the jet, where the electron distribution is obtained by numerically solving the evolution equation along the jet self-consistently. For comparison, we also apply the model to Mrk 421 and Mrk 501, which are the potential candidates for the hard TeV emissions. We demonstrate that the model can satisfactorily reproduce the spectral energy distributions of eight sources, particularly of six Hard-TeV sources, where no extreme minimum Lorentz factor of the electron population is required. In contrast with Mrk 421 and Mrk 501, six Hard-TeV sources have rather low magnetization in emitting regions and high cutoff energies of the electron distributions.
Solar Supergranular Fractal Dimension Dependence on the Solar Cycle Phase
Authors: Rajani G. , Sowmya G. M. , Paniveni U. , Srikanth R.
Published: January 2022

We study the complexity of the supergranular network through fractal dimension by using the Ca ii K digitized data archive obtained from the Kodaikanal Solar Observatory. The data consist of 326 visually selected supergranular cells spread across the 23rd solar cycle. Only cells that were well-defined were chosen for the analysis and we discuss the potential selection effect thereof, mainly that it favors cells of a smaller size (<20 Mm). Within this sample, we analyzed the fractal dimension of supergranules across the solar cycle and find that it is anticorrelated with the activity level.
Oocyte mitochondria—key regulators of oocyte function and potential therapeutic targets for improving fertility
Authors: Adhikari Deepak , Lee In-won , Yuen Wai Shan , Carroll John
Published: January 2022

The development of oocytes and early embryos is dependent on mitochondrial ATP production. This reliance on mitochondrial activity, together with the exclusively maternal inheritance of mitochondria in development, places mitochondria as central regulators of both fertility and transgenerational inheritance mechanisms. Mitochondrial mass and mtDNA content massively increase during oocyte growth. They are highly dynamic organelles and oocyte maturation is accompanied by mitochondrial trafficking around subcellular compartments. Due to their key roles in generation of ATP and reactive oxygen species (ROS), oocyte mitochondrial defects have largely been linked with energy deficiency and oxidative stress. Pharmacological treatments and mitochondrial supplementation have been proposed to improve oocyte quality and fertility by enhancing ATP generation and reducing ROS levels. More recently, the role of mitochondria-derived metabolites in controlling epigenetic modifiers has provided a mechanistic basis for mitochondria–nuclear crosstalk, allowing adaptation of gene expression to specific metabolic states. Here, we discuss the multi-faceted mechanisms by which mitochondrial function influence oocyte quality, as well as longer-term developmental events within and across generations.
Endometrial and luteal responses to a prostaglandin F2alpha pulse: a comparison between heifers and mares
Authors: Domingues Rafael R , Ginther O J , Gomez-Leon Victor , Castro Thadeu , Wiltbank Milo C
Published: January 2022

In heifers and mares, multiple pulses of prostaglandin F2alpha (PGF) are generally associated with complete luteal regression. Although PGF pulses occur before and during luteolysis, little is known about the role of minor PGF pulses during preluteolysis on subsequent luteal and endometrial PGF production that may initiate luteolysis. Heifers (n = 7/group) and mares (n = 6/group) were treated with a single minor dose of PGF (3.0 and 0.5 mg, respectively) during mid-luteal phase (12 and 10 days postovulation respectively). After treatment, a transient decrease in progesterone (P4) concentrations occurred in heifers between Hours 0 and 2 but at Hour 4 P4 was not different from pretreatment. In mares, P4 was unaltered between Hours 0 and 4. Concentrations of P4 decreased in both species by Hour 24 and complete luteolysis occurred in mares by Hour 48. Luteal and endometrial gene expression were evaluated 4 h posttreatment. In heifers, luteal mRNA abundance of PGF receptor and PGF dehydrogenase was decreased, while PTGS2, PGF transporter, and oxytocin receptor were increased. In the heifer endometrium, receptors for oxytocin, P4, and estradiol were upregulated. In mares, luteal expression of PGF receptor was decreased, while PGF transporter and oxytocin receptor were increased. The decrease in P4 between Hours 4 and 24 and changes in gene expression were consistent with upregulation of endogenous synthesis of PGF. The hypotheses were supported that a single minor PGF treatment upregulates endogenous machinery for PGF synthesis in heifers and mares stimulating endogenous PGF synthesis through distinct regulatory mechanisms in heifers and mares.
Formation and function of dauer ascarosides in the nematodes Caenorhabditis briggsae and Caenorhabditis elegans
Authors: Cohen Sarah M , Wrobel Chester J J , Prakash Sharan J , Schroeder Frank C , Sternberg Paul W
Published: January 2022

The biosynthetic pathways and functions of ascaroside signaling molecules in the nematode Caenorhabditis elegans have been studied to better understand complex, integrative developmental decision-making. Although it is known that ascarosides play multiple roles in the development and behavior of nematode species other than C. elegans, these parallel pheromone systems have not been well-studied. Here, we show that ascarosides in the nematode Caenorhabditis briggsae are biosynthesized in the same manner as C. elegans and act to induce the alternative developmental pathway that generates the stress-resistant dauer lifestage. We show that ascr#2 is the primary component of crude dauer pheromone in C. briggsae; in contrast, C. elegans dauer pheromone relies on a combination of ascr#2, ascr#3, and several other components. We further demonstrate that Cbr-daf-22, like its C. elegans ortholog Cel-daf-22, is necessary to produce short-chain ascarosides. Moreover, Cbr-daf-22 and Cel-daf-22 mutants produce an ascaroside-independent metabolite that acts antagonistically to crude dauer pheromone and inhibits dauer formation.
Objectively Measured Total Sedentary Time and Pattern of Sedentary Accumulation in Older Adults: Associations With Incident Cardiovascular Disease and All-Cause Mortality
Authors: Yerramalla Manasa Shanta , van Hees Vincent T , Chen Mathilde , Fayosse Aurore , Chastin Sebastien F M , Sabia Séverine
Published: January 2022

Background

We examined associations of total duration and pattern of accumulation of objectively measured sedentary behavior (SB) with incident cardiovascular disease (CVD) and all-cause mortality among older adults.

Methods

Total sedentary time and 8 sedentary accumulation pattern metrics were extracted from accelerometer data of 3 991 Whitehall II study participants aged 60–83 years in 2012–2013. Incident CVD and all-cause mortality were ascertained up to March 2019.

Results

Two hundred and ninety-nine CVD cases and 260 deaths were recorded over a mean (standard deviation [SD]) follow-up of 6.2 (1.3) and 6.4 (0.8) years, respectively. Adjusting for sociodemographic and behavioral factors, 1-SD (100.2 minutes) increase in total sedentary time was associated with 20% higher CVD risk (hazard ratio [95% confidence interval]: 1.20 [1.05–1.37]). More fragmented SB was associated with reduced CVD risk (eg, 0.86 [0.76–0.97] for 1-SD [6.2] increase in breaks per sedentary hour). Associations were not evident once health-related factors and moderate-to-vigorous physical activity (MVPA) were considered. For all-cause mortality, associations with more fragmented SB (eg, 0.73 [0.59–0.91] for breaks per sedentary hour) were found only among the youngest older group (<74 years; p for interaction with age < .01) independently from all covariates.

Conclusions

In this study, no associations of total sedentary time and sedentary accumulation patterns with incident CVD and all-cause mortality were found in the total sample once MVPA was considered. Our findings of reduced mortality risk with less total and more fragmented SB independent from MVPA among individuals <74 years need to be replicated to support the recent recommendations to reduce and fragment SB.
Algorithm Design for a Cytokine Release Assay of Antigen-Specific In Vitro Stimuli of Circulating Leukocytes to Classify Leprosy Patients and Household Contacts
Authors: Marçal Pedro Henrique Ferreira , de Souza Márcio Luís Moreira , Gama Rafael Silva , de Oliveira Lorena Bruna Pereira , Gomes Matheus de Souza , do Amaral Laurence Rodrigues , Pinheiro Roberta Olmo , Sarno Euzenir Nunes , Moraes Milton Ozório , Fairley Jessica K , Martins-Filho Olindo Assis , de Oliveira Fraga Lucia Alves
Published: January 2022

Background

Immunological biomarkers have often been used as a complementary approach to support clinical diagnosis in several infectious diseases. The lack of commercially available laboratory tests for conclusive early diagnosis of leprosy has motivated the search for novel methods for accurate diagnosis. In the present study, we describe an integrated analysis of a cytokine release assay using a machine learning approach to create a decision tree algorithm. This algorithm was used to classify leprosy clinical forms and monitor household contacts.

Methods

A model of Mycobacterium leprae antigen-specific in vitro assay with subsequent cytokine measurements by enzyme-linked immunosorbent assay was employed to measure the levels of tumor necrosis factor (TNF), interferon-γ, interleukin 4, and interleukin 10 (IL-10) in culture supernatants of peripheral blood mononuclear cells from patients with leprosy, healthy controls, and household contacts. Receiver operating characteristic curve analysis was carried out to define each cytokine’s global accuracy and performance indices to identify clinical subgroups.

Results

Data demonstrated that TNF (control culture [CC]: AUC = 0.72; antigen-stimulated culture [Ml]: AUC = 0.80) and IL-10 (CC: AUC = 0.77; Ml: AUC = 0.71) were the most accurate biomarkers to classify subgroups of household contacts and patients with leprosy, respectively. Decision tree classifier algorithms for TNF analysis categorized subgroups of household contacts according to the operational classification with moderate accuracy (CC: 79% [48/61]; Ml: 84% [51/61]). Additionally, IL-10 analysis categorized leprosy patients’ subgroups with moderate accuracy (CC: 73% [22/30] and Ml: 70% [21/30]).

Conclusions

Together, our findings demonstrated that a cytokine release assay is a promising method to complement clinical diagnosis, ultimately contributing to effective control of the disease.
Circadian rhythm disruption results in visual dysfunction
Authors: Mathew Deepa , Luo Qianyi , Bhatwadekar Ashay D.
Published: January 2022

Artificial light has been increasingly in use for the past 70 years. The aberrant light exposure and round‐the‐clock nature of work lead to the disruption of biological clock. Circadian rhythm disruption (CRD) contributes to multiple metabolic and neurodegenerative diseases. However, its effect on vision is not understood. Moreover, the mammalian retina possesses an autonomous clock that could be reset with light exposure. We evaluated the impact of CRD on retinal morphology, physiology, and vision after housing mice in a disruption inducing shorter light/dark cycle (L10:D10). Interestingly, the mice under L10:D10 exhibited three different entrainment behaviors; “entrained,” “free‐running,” and “zigzagging.” These behavior groups under CRD exhibited reduced visual acuity, retinal thinning, and a decrease in the number of photoreceptors. Intriguingly, the electroretinogram response was decreased only in the mice exhibiting “entrained” behavior. The retinal proteome showed distinct changes with each entrainment behavior, and there was a dysfunctional oxidative stress‐antioxidant mechanism. These results demonstrate that CRD alters entrainment behavior and leads to visual dysfunction in mice. Our studies uniquely show the effect of entrainment behavior on retinal physiology. Our data have broader implications in understanding and mitigating the impact of CRD on vision and its potential role in the etiology of retinal diseases.
Acute Pain Management for a Tibial Plateau Fracture Shortly After a Buprenorphine XR Depot Injection: A Case Report
Authors: Sivanathan Lavarnan , Logan Elizabeth , Popovski Katherine , Goel Akash , Hauck Tanya , Ladha Karim S.
Published: January 2022

Acute pain management of patients on buprenorphine for opioid use disorder remains a challenge. The buprenorphine extended-release depot injection which lasts for 1 month and has a higher plasma concentration of buprenorphine compared to the sublingual formulation is increasingly being used in patients. Acute pain management of patients on buprenorphine depot remains a challenge because waiting for the washout of the medication is not feasible and discontinuation is challenging because it requires surgical excision. We describe here the pharmacokinetics of the buprenorphine depot formulation and the clinical implications of its long duration of action. A 39-year-old woman with a history of alcohol and opioid use disorder, on buprenorphine depot, was admitted to the hospital with a left tibial plateau fracture. Acute pain service managed her pain by utilizing a multimodal analgesia plan including femoral and popliteal nerve catheters, intravenous patient-controlled analgesia and oral opioid and nonopioid medications. The patient had a prolonged length of stay of 11 days but was successfully weaned off nerve catheters and intravenous medications and converted to an oral medication regiment such that she could be discharged from the acute care hospital.
Efficacy of transcutaneous tibial nerve stimulation in the treatment of bladder pain syndrome
Authors: Alkis Okan , Aras Bekir , Sevim Mehmet , Kartal İbrahim Güven , Sönmez Oğuzhan Yusuf , İvelik Halil İbrahim
Published: January 2022

Background:

This study aimed to demonstrate the effectiveness of transcutaneos tibial nerve stimulation (TTNS) in the treatment of bladder pain syndrome (BPS).

Materials and methods:

The data of 16 female patients, diagnosed with BPS in our clinic between 2019 and 2021 and had TTNS twice a week for 12 weeks, were retrospectively analyzed.

Results:

The mean age of the patients was 46.00 ± 13.11 years, and the mean body mass index was 26.43 ± 3.07 kg/m2. After the treatment, the median day time frequency of the patients decreased from 13.37 (3.69) to 10.25 (4.56) (p 
< 0.001). Nocturia also decreased after treatment from 4.37 (1.81) to 3.00 (1.94) (p 
= 0.001). The median voiding volume increased by 26.5 mL (p 
= 0.001). The median of the patients’ visual analog scale scores decreased after treatment (median of visual analog scale score changed from interquartile range 8 [1] to 7 [4]) (p 
= 0.001). In addition, the median interquartile range interstitial cystitis symptom index scores decreased from 17 (4) to 15 (10) (p = 0.002).

Conclusions:

In this study it was demonstrated that TTNS is an alternative method that can be successfully applied before invasive methods in the treatment of BPS.
Construction and application of time-effect assessment database for experiments on war-traumatized animals
Authors: Wang Junkang , Wang Jing , Zhang Hongliang , Guo Chengyu , Wang Yanbiao , Lu Bing , Feng Cong , Pan Fei , Li Tanshi
Published: January 2022

Background

High-quality real war trauma data are important, but they are still lacking. Using the database to realize the networked, systematic, standardized, and dynamic management of war injury animal experimental data can provide a real and reliable supplement for the research of war injury treatment.

Methods

Through demand analysis, module design, architecture design, compilation and debugging, and other processes, JAVA language development tools were used to develop a time-effect assessment database for experiments on war-traumatized animals, where the browser/server architecture (B/S architecture) is used as the technical architecture and SQL Server as the database management system.

Results

A time-effect assessment database for experiments on war-traumatized animals that features reasonable structural design, rich data resources, and convenient use has been established, in which case efficient collection, storage, display, retrieval, and management of animal experimental data have been achieved. At present, the database is running well and has good data quality.
Drug–Drug Interactions With Cyclosporine in the Anti-Hepatitis C Viral PrOD Combination Regimen of Paritaprevir/Ritonavir–Ombitasvir and Dasabuvir in Organ Transplant Recipients With Severe Hepatic Fibrosis or Cirrhosis
Authors: Huang Ying-Yu , Huang Yu-Hsuan , Wu Tsai-Hung , Loong Che-Chuan , Hsu Chia-Chen , Chou Yueh-Ching , Chang Yuh-Lih
Published: January 2022

Background:

The clinical guidelines suggest that the dosing of cyclosporine (CsA), during combination therapy with paritaprevir/ritonavir–ombitasvir and dasabuvir (PrOD), would be only one-fifth of the pre-PrOD total daily dose to be administered once daily. However, this dosing may not be applicable to all patients depending on their clinical condition. This study focuses on the pharmacokinetic dynamics of PrOD with CsA in Asian organ transplant recipients with severe liver fibrosis or cirrhosis who undergo concurrent treatment with PrOD treatment and CsA. The efficacy and safety of PrOD treatment was also evaluated.

Methods:

Data from 7 patients obtained between January 2017 and September 2017 were retrospectively analyzed. Determinations of the blood concentrations of CsA were made, whether used as a single treatment or in combination therapy with PrOD.

Results:

The combination regimen compared with CsA administered alone resulted in a 4.53-fold and 5.52-fold increase in the area under the concentration–time curve from time 0–12 hours (AUC0–12 h) of CsA on days 1 and 15, respectively. In addition, the maximal concentration, time to maximum concentration, and terminal phase elimination half-life (t1/2) of CsA were increased during the combined treatment of PrOD and CsA. The authors proposed reducing the CsA dosage during PrOD treatment to one-seventh of that of the pre-PrOD treatment of the total daily dose to maintain target CsA levels. All patients achieved sustained virologic responses at week 12. There were no episodes of serious adverse events or graft rejections observed.

Conclusions

Although the combination with PrOD significantly affects the pharmacokinetics of CsA, it is effective and safe with regular monitoring of the CsA blood concentrations and appropriate CsA dose adjustment.
Distinguishing Multisystem Inflammatory Syndrome in Children From COVID-19, Kawasaki Disease and Toxic Shock Syndrome
Authors: Godfred-Cato Shana , Abrams Joseph Y. , Balachandran Neha , Jaggi Preeti , Jones Kaitlin , Rostad Christina A. , Lu Austin T. , Fan Lucie , Jabbar Aysha , Anderson Evan J. , Kao Carol M. , Hunstad David A. , Rosenberg Robert B. , Zafferani Marc J. , Ede Kaleo C. , Ballan Wassim , Laham Federico R. , Beltran Yajira , Bryant Bobbi , Meng Lu , Hammett Teresa A. , Oster Matthew E. , Bamrah Morris Sapna , Belay Ermias D.
Published: January 2022

Background:

Distinguishing multisystem inflammatory syndrome in children (MIS-C) from coronavirus disease 2019 (COVID-19), Kawasaki disease (KD), and toxic shock syndrome (TSS) can be challenging. Because clinical management of these conditions can vary, timely and accurate diagnosis is essential.

Methods:

Data were collected from patients <21 years of age hospitalized with MIS-C, COVID-19, KD, and TSS in 4 major health care institutions. Patient demographics and clinical and laboratory data were compared among the 4 conditions, and a diagnostic scoring tool was developed to assist in clinical diagnosis.

Results:

A total of 233 patients with MIS-C, 102 with COVID-19, 101 with KD, and 76 with TSS were included in the analysis. Patients with MIS-C had the highest prevalence of decreased cardiac function (38.6%), myocarditis (34.3%), pericardial effusion (38.2%), mitral regurgitation (31.8%) and pleural effusion (34.8%) compared with patients with the other conditions. Patients with MIS-C had increased peak levels of C-reactive protein and decreased platelets and lymphocyte nadir counts compared with patients with COVID-19 and KD and elevated levels of troponin, brain natriuretic peptide and pro-brain natriuretic peptide compared with COVID-19. Diagnostic scores utilizing clinical findings effectively distinguished MIS-C from COVID-19, KD, and TSS, with internal validation showing area under the curve ranging from 0.87 to 0.97.

Conclusions:

Compared with COVID-19, KD, and TSS, patients with MIS-C had significantly higher prevalence of cardiac complications, elevated markers of inflammation and cardiac damage, thrombocytopenia, and lymphopenia. Diagnostic scores can be a useful tool for distinguishing MIS-C from COVID-19, KD, and TSS.
Clinical Presentations and Outcomes of Children in Canada With Recurrent Invasive Pneumococcal Disease From the IMPACT Surveillance Network
Authors: Murad Yousif , Hung Te-Yu , Sadarangani Manish , Morris Shaun K. , Le Saux Nicole , Vanderkooi Otto G. , Kellner James D. , Tyrrell Gregory J. , Martin Irene , Demczuk Walter , Halperin Scott A. , Bettinger Julie A. ,   for the Members of IMPACT,   * Investigators participating in this IMPACT project included:, Bridger N. , Foo Cheryl , Halperin S.A. , Top K.A. , Thibeault R. , Moore D. , Papenburg J. , Lebel M. , Le Saux N. , Morris S. , Embree J. , Tan B. , McConnell Athena , Jadavji T. , Constantinescu C. , Vaudry W. , Scheifele D. , Sadarangani M. , Bettinger J. , Sauvé L.
Published: January 2022

Background:

Invasive pneumococcal disease due to Streptococcus pneumoniae can cause mortality and severe morbidity due to sepsis, meningitis and pneumonia, particularly in young children and the elderly. Recurrent invasive pneumococcal disease is rare yet serious sequelae of invasive pneumococcal disease that is associated with the immunocompromised and leads to a high mortality rate.

Method:

This retrospective study reviewed recurrent invasive pneumococcal disease cases from the Canadian Immunization Monitoring Program, ACTive (IMPACT) between 1991 and 2019, an active network for surveillance of vaccine-preventable diseases and adverse events following immunization for children ages 0–16 years. Data were collected from 12 pediatric tertiary care hospitals across all 3 eras of public pneumococcal conjugate vaccine implementation in Canada.

Results:

The survival rate within our cohort of 180 recurrent invasive pneumococcal disease cases was 98.3%. A decrease of 26.4% in recurrent invasive pneumococcal disease due to vaccine serotypes was observed with pneumococcal vaccine introduction. There was also a 69.0% increase in the rate of vaccination in children with preexisting medical conditions compared with their healthy peers.

Conclusion:

The decrease in recurrent invasive pneumococcal disease due to vaccine-covered serotypes has been offset by an increase of non-vaccine serotypes in this sample of Canadian children.
Association Between Real-time Polymerase Chain Reaction Cycle Threshold Value and Clinical Severity in Neonates and Infants Infected With Bordetella pertussis
Authors: Thuy Nga Do Thi , Thi Bich Thuy Phung , Ainai Akira , Takayama Ikuyo , Huong Do Thu , Saitoh Aya , Nakagawa Satoshi , Minh Dien Tran , Nakajima Noriko , Saitoh Akihiko
Published: January 2022

Background:

Polymerase chain reaction (PCR) is highly sensitive and is thus the standard method for diagnosing pertussis. Real-time PCR is widely used because of its accuracy and the simplicity of the simultaneous cycle threshold (Ct) value, which represents the copy numbers of the target gene. Little is known of the association of Ct value with pertussis severity in neonates and infants.

Methods:

This study determined Ct values in neonates and infants diagnosed with pertussis by real-time PCR using nasopharyngeal samples at Vietnam National Children’s Hospital in Hanoi in 2017 and 2019. The association of disease severity and clinical parameters were analyzed using univariate and multivariate analyses.

Results:

We evaluated 108 patients with pertussis [median age: 63 days, interquartile range (IQR): 41–92 days]. Only 6/108 (6%) received at least 1 dose of a pertussis-containing vaccine. Among them, 24 (22.2%) had severe disease requiring care in a pediatric intensive care unit, 16 (13.8%) required mechanical ventilation, and 3 (2.6%) died. The median Ct value was lower in patients with severe disease (19.0, IQR: 16.5–22.0, n = 24) than in those without severe disease (25.5, IQR: 20.0–30.0, n = 84) (P = 0.002). Logistic regression analyses demonstrated that PCR Ct value [odds ratio (OR): 1.783, 95% confidence interval (CI): 1.013–3.138, P = 0.045], age (OR: 3.118, 95% CI: 1.643–5.920, P = 0.001), and white blood cell counts (OR: 0.446, 95% CI: 0.261–0.763, P = 0.003) remained significantly associated with severe disease.

Conclusions:

Real-time PCR Ct values for pertussis might be useful as a predictor of severe disease in neonates and infants.
NonTuberculous Mycobacteria Blood Stream Infection in Pediatric and Adult Patients
Authors: Dabaja-Younis Halima , Damouni-Shalabi Ranaa , Ganem-Zoubi Nesrin , Shachor-Meyouhas Yael , Hussein Khetam , Geffen Yuval , Kassis Imad
Published: January 2022

Background:

Nontuberculous Mycobacteria (NTM) are rare causes of bloodstream infection (BSI). This study addresses the management and prognosis of NTM BSI and the differences between adult and pediatric patients.

Methods:

We retrospectively reviewed the medical charts of patients at any age with NTM BSI, from January 1, 2005, to June 30, 2020. Data on demographics, underlying conditions, clinical manifestations, NTM species, antibiotic treatments and outcomes were retrieved.

Results:

Positive blood cultures for NTM were detected in 43 patients, 30 children and 13 adults. Median age: 10.37 years (IQR 6.692–39.864). Thirty-seven (86%) patients had an active malignant disease. Fever was the chief sign in 23 (53.5%) patients and pulmonary manifestations in 14 (32.6%). Rapidly growing NTM comprised 39 (90.7%) of the isolates. Central venous catheter (CVC) was documented in 39 (90.7%) cases, 31 (79.5%) of which were removed as part of treatment. Antibiotic treatment directed against NTM was documented in 26 (60.5%) patients. CVC was removed in 7/17 patients who were not treated with antibiotics. Relapse occurred in 3 cases; no 30-days mortality was reported. Children and adults had similar clinical characteristics. However, children had a higher rate of CVC at the time of bacteremia and a higher chance to receive treatment.

Conclusion:

NTM BSI was seen mainly in oncologic patients with CVC. Children and adults had a similar disease course and outcome. Relapse was rare and NTM-related mortality was not reported.