bluuebunny/crossref_metadata_2025 huggingface dataset:
Adverse Events Associated With Treatment for Pan-Susceptible Tuberculosis in San Francisco
Authors: Louie Janice K , Keh Chris , Agraz-Lara Rocio , Phillips Allison , Graves Susannah
Published: November 2022

Of 373 patients treated for drug-susceptible tuberculosis, 35.4% (46.2% aged ≥65 years) developed moderate/severe adverse events that required treatment interruption (34.8%), first-line drug discontinuation (26.2%, primarily pyrazinamide), second-line drug initiation (30.0%), and treatment duration up to 3.8 months longer. More safe and effective options are needed, including for the elderly.
Liquid Biopsy and Immuno-Oncology for Advanced Nonsmall Cell Lung Cancer
Authors: Sinoquet Léa , Jacot William , Quantin Xavier , Alix-Panabières Catherine
Published: November 2022

Background

In the last decade, immune checkpoint inhibitors have revolutionized the treatment of metastatic nonsmall cell lung cancer without oncogenic addiction. Currently, programmed death ligand 1 (PD-L1) status, assessed in tissue biopsy samples, is the only test for guiding the prescription of these therapies in clinical practice. However, obtaining tumor tissue from patients with lung cancer is not always feasible and PD-L1 positivity is not a guarantee of immunotherapy efficacy. In this context, liquid biopsy, represented by several circulating biomarkers that reflect the tumor characteristics, is emerging as an interesting alternative approach.

Content

We describe the main blood biomarkers evaluated in patients with metastatic nonsmall cell lung cancer before/during immune checkpoint inhibitor treatment, with a focus on circulating cell-free DNA, circulating tumor DNA (ctDNA), blood tumor mutational burden, and circulating tumor cells (CTCs).

Monitoring of ctDNA and CTCs during immunotherapy may be a promising tool to help clinicians in therapeutic decision-making.
Olfaction and reaction: The role of olfactory and hypothalamic investment in the antipredator responses to chemical alarm cues by northern redbelly dace
Authors: Joyce Brendan J , Brown Grant E
Published: November 2022

Neuroplasticity enables teleosts to promote or downregulate the growth of their brains regionally. To compensate for the effects of predation pressure, teleosts may alter their brain morphology and behavioral responses to mitigate its impact on individual fitness. High-predation environments often promote specific patterns of brain growth and produce bolder and more proactive populations. Owing to the expense of maintaining neural tissue, relative size indicates the regions most relied upon. In northern redbelly dace Chrosomus eos, as little as 2 weeks of elevated predation pressure, resulted in increased investment in their olfactory bulbs and optic tecta, while the imposition of captivity produced smaller, less symmetric hypothalami. Taken together, these results suggest that an individual could potentially become better able to detect a threat, and simultaneously less inclined to react to it, making the impact of either change in isolation is difficult to discern. Here, we compared interindividual variation in gross brain morphology, risk-taking tactics in a novel arena (shy–bold personality), and responding to olfactory cues (proactive/reactive stress-coping style). We hypothesized that olfactory investment would positively correlate with response intensity to predator cue concentration and respond across a wider range of cue concentrations, while hypothalamus size would correlate with shyness and reactivity. Exposure to heightened risk produced more bold/proactive individuals, with larger olfactory bulbs and smaller hypothalami. However, the direction of the correlation between hypothalamus size and behavior varied by treatment, and olfactory investment only corresponded with response intensity amongst proactive individuals. Our findings illustrate the potential pitfalls of relating gross brain morphology to complex behavior and suggest that stress-coping style is a relevant consideration in future studies.
Post-inflammatory Polyp Burden as a Prognostic Marker of Disease-outcome in Patients with Inflammatory Bowel Disease
Authors: Ellul Pierre , Schembri John , Vella Baldacchino Andrea , Molnár Tamas , Resal Tamas , Allocca Mariangela , Furfaro Federica , Dal Buono Arianna , Theodoropoulou Angeliki , Fragaki Maria , Tsoukali Emmanouela , Mantzaris Gerassimos J , Phillips Frank M , Radford Shellie , Moran Gordon , Gonzalez Haidee , Sebastian Shaji , Fousekis Fotios , Christodoulou Dimitrios , Snir Ifat , Lerner Zlata , Yanai Henit , Michalopoulos Georgios , Tua Julia , Camilleri Liberato , Papamichael Kostas , Karmiris Konstantinos , Katsanos Konstantinos
Published: November 2022

Background and Aims

Post-inflammatory polyps [PIPs] are considered as indicators of previous episodes of severe inflammation and mucosal ulceration. Inflammatory bowel disease [IBD], namely Crohn’s disease [CD] and ulcerative colitis [UC], exhibit a perpetuating, relapsing and remitting pattern, and PIPs are a frequent sequela of chronicity. The aim of this study was to determine whether a high PIP burden is associated with a more severe disease course in patients with IBD.

Methods

This was a multinational, multicentre, retrospective study. IBD patients previously diagnosed with PIPs were retrieved from the endoscopic database of each centre. PIP burden was evaluated and associated with demographic and clinical data as well as factors indicating a more unfavourable disease course.

Results

A total of 504 IBD patients with PIPs were recruited [male: 61.9%]. The mean age at IBD diagnosis was 36.9 [±16.8] years. Most patients [74.8%] were diagnosed with UC. A high PIP burden was present in 53.4% of patients. On multivariable Cox regression analysis, a high PIP burden was independently associated with treatment escalation (hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.04–1.75; p = 0.024), hospitalization [HR 1.90; 95% CI 1.24–2.90; p = 0.003], need for surgery [HR 2.28; 95% CI 1.17–4.44, p = 0.02] and younger age at diagnosis [HR 0.99, 95% CI 0.98–0.99; p = 0.003].

Conclusion

PIP burden was associated with a more severe outcome. Future prospective studies should focus on the characterization of PIP burden as to further risk stratify this patient cohort.
Remote dielectric sensing to detect acute heart failure in patients with dyspnoea: a prospective observational study in the emergency department
Authors: Olesen Anne Sophie Overgaard , Miger Kristina , Fabricius-Bjerre Andreas , Sandvang Kathrine Dyrsting , Kjesbu Ingunn Eklo , Sajadieh Ahmad , Høst Nis , Køber Nana , Wamberg Jesper , Pedersen Lars , Schultz Hans Henrik Lawaetz , Abild-Nielsen Annemette Geilager , Wille Mathilde Marie Winkler , Nielsen Olav Wendelboe
Published: November 2022

Aims

Remote dielectric sensing (ReDS) enables quick estimation of lung fluid content. To examine if ReDS is superior to other methods in detecting acute heart failure.

Methods and results

We included consecutive patients with dyspnoea from the emergency departments at Bispebjerg Hospital, Copenhagen, and performed ReDS, low-dose chest computed tomography (CT), echocardiogram, lung ultrasound, NT-Pro-brain natriuretic peptide (NT-proBNP), and a Boston score evaluation (chest X-ray and clinical signs). ReDS values >35% were used as a cut-off to diagnose pulmonary congestion. Acute heart failure was adjudicated by experts’ review of health records but independently of ReDS values. Sub-analyses investigated ReDS in acute heart failure patients with congestion on CT. We included 97 patients within a median of 4.8 h from admittance: 25 patients (26%) were ReDS-positive and 39 (40%) had adjudicated acute heart failure (21 with and 18 without CT congestion). Heart failure patients had median ReDS 33%, left ventricular ejection fraction 48%, and NT-proBNP 2935 ng/L. A positive ReDS detected heart failure with 46% sensitivity, 88% specificity, and 71% accuracy. The AUC for ReDS was like the Boston score (P = 0.88) and the lung ultrasound score (P = 0.74). CT-congested heart failure patients had higher ReDS values than patients without heart failure (median 38 vs. 28%, P < 0.001). Heart failure patients without CT-congestion had ReDS values like patients without heart failure (mean 30 vs. 28%, P = 0.07).

Conclusion

ReDS detects acute heart failure similarly to the Boston score and lung ultrasound score, and ReDS primarily identifies the acute heart failure patients who have congestion on a chest CT.
Effect of all-but-one conditional analysis for eQTL isolation in peripheral blood
Authors: Brown Margaret , Greenwood Emily , Zeng Biao , Powell Joseph E , Gibson Greg
Published: November 2022

Expression quantitative trait locus detection has become increasingly important for understanding how noncoding variants contribute to disease susceptibility and complex traits. The major challenges in expression quantitative trait locus fine-mapping and causal variant discovery relate to the impact of linkage disequilibrium on signals due to one or multiple functional variants that lie within a credible set. We perform expression quantitative trait locus fine-mapping using the all-but-one approach, conditioning each signal on all others detected in an interval, on the Consortium for the Architecture of Gene Expression cohorts of microarray-based peripheral blood gene expression in 2,138 European-ancestry human adults. We contrast these results with traditional forward stepwise conditional analysis and a Bayesian localization method. All-but-one conditioning significantly modifies effect-size estimates for 51% of 2,351 expression quantitative trait locus peaks, but only modestly affects credible set size and location. On the other hand, both conditioning approaches result in unexpectedly low overlap with Bayesian credible sets, with just 57% peak concordance and between 50% and 70% SNP sharing, leading us to caution against the assumption that any one localization method is superior to another. We also cross reference our results with ATAC-seq data, cell-type-specific expression quantitative trait locus, and activity-by-contact-enhancers, leading to the proposal of a 5-tier approach to further reduce credible set sizes and prioritize likely causal variants for all known inflammatory bowel disease risk loci active in immune cells.
Expanded FLP toolbox for spatiotemporal protein degradation and transcriptomic profiling in Caenorhabditis elegans
Authors: Fragoso-Luna Adrián , Romero-Bueno Raquel , Eibl Michael , Ayuso Cristina , Muñoz-Jiménez Celia , Benes Vladimir , Cases Ildefonso , Askjaer Peter
Published: November 2022

Control of gene expression in specific tissues and/or at certain stages of development allows the study and manipulation of gene function with high precision. Site-specific genome recombination by the flippase (FLP) and cyclization recombination (Cre) enzymes has proved particularly relevant. Joint efforts of many research groups have led to the creation of efficient FLP and Cre drivers to regulate gene expression in a variety of tissues in Caenorhabditis elegans. Here, we extend this toolkit by the addition of FLP lines that drive recombination specifically in distal tip cells, the somatic gonad, coelomocytes, and the epithelial P lineage. In some cases, recombination-mediated gene knockouts do not completely deplete protein levels due to persistence of long-lived proteins. To overcome this, we developed a spatiotemporally regulated degradation system for green fluorescent fusion proteins based on FLP-mediated recombination. Using 2 stable nuclear pore proteins, MEL-28/ELYS and NPP-2/NUP85 as examples, we report the benefit of combining tissue-specific gene knockout and protein degradation to achieve complete protein depletion. We also demonstrate that FLP-mediated recombination can be utilized to identify transcriptomes in a C. elegans tissue of interest. We have adapted RNA polymerase DamID for the FLP toolbox and by focusing on a well-characterized tissue, the hypodermis, we show that the vast majority of genes identified by RNA polymerase DamID are known to be expressed in this tissue. These tools allow combining FLP activity for simultaneous gene inactivation and transcriptomic profiling, thus enabling the inquiry of gene function in various complex biological processes.
Life-Course Trajectories of Risk-Taking Propensity: A Coordinated Analysis of Longitudinal Studies
Authors: Liu Yunrui , Bagaïni Alexandra , Son Gayoung , Kapoor Madlaina , Mata Rui
Published: November 2022

Objectives

How does risk preference change across the life span? We address this question by conducting a coordinated analysis to obtain the first meta-analytic estimates of adult longitudinal age differences in risk-taking propensity in different domains.

Methods

We report results from 26 longitudinal samples (12 panels; 187,733 unique respondents; 19 countries) covering general and domain-specific risk-taking propensity (financial, driving, recreational, occupational, health) across 3 or more waves.

Results

Results revealed a negative relation between age and both general and domain-specific risk-taking propensity. Furthermore, females consistently reported lower levels of risk taking across the life span than males in all domains, but there is little support for the idea of an age by gender interaction. Although we found evidence of systematic and universal age differences, we also detected considerable heterogeneity across domains and samples.

Discussion

Our work suggests a need to understand the nature of heterogeneity of age differences in risk-taking propensity and recommends the use of domain-specific and population estimates for applications interested in modeling heterogeneity in risk preference for economic and policy-making purposes.
Mandated Caregiver Training in the Veterans Health Administration: Caregiver Inquiry Informs National Dissemination
Authors: Sperber Nina R , Boucher Nathan , Hughes Jaime M , Bruening Rebecca , Zullig Leah L , Decosimo Kasey , Tucker Matthew , Christensen Leah A , Allen Kelli D , Hastings Susan N , Van Houtven Courtney H
Published: November 2022

Background and Objectives

A minority of family caregivers receive training, with implications for their own and their recipient’s outcomes. Federal policy has supported the implementation and expansion of caregiver training and support. The Department of Veterans Affairs (VA) has developed a national Caregiver Support Program and collaborated with VA health services researchers to explore caregivers’ acceptance of an evidence-based training program in preparation for system-wide dissemination.

Research Design and Methods

This approach entailed a convergent mixed-methods design, which involved separate analyses of quantitative and qualitative data. Survey questions based on the Kirkpatrick model for training evaluation measured caregivers’ reaction and learning, and interview questions elicited caregivers’ reports about the value of the program for them.

Results

Most caregivers reported satisfaction with the training when responding to survey questions, although qualitative interviews revealed caveats suggesting need to hone the best timing and specific group of caregivers for maximal benefit.

Discussion and Implications

Our findings indicate that understanding program–user fit may be particularly critical when implementing training for caregivers as they come to the program at different points along their caregiving journey, needing differing types and intensities of support. While a general program may appeal to policymakers aiming to scale caregiver training within a large, heterogeneous system, there may be shortcomings in terms of end-user acceptance and subsequent downstream outcomes such as reach and ultimately program effectiveness. Good, iterative communication flow between program developers and policymakers facilitates this understanding and, in turn, decisions about scaling.
Transcription factor FoxM1 promotes cyst growth in PKD1 mutant ADPKD
Authors: Yu Wenyan , Wang Guojuan , Li Linda Xiaoyan , Zhang Hongbing , Gui Xuehong , Zhou Julie Xia , Calvet James P , Li Xiaogang
Published: November 2022

Autosomal dominant polycystic kidney disease (ADPKD) is driven by mutations in the PKD1 and PKD2 genes, and it is characterized by renal cyst formation, inflammation and fibrosis. Forkhead box protein M1 (FoxM1), a transcription factor of the Forkhead box (Fox) protein super family, has been reported to promote tumor formation, inflammation and fibrosis in many organs. However, the role and mechanism of FoxM1 in regulation of ADPKD progression is still poorly understood. Here, we show that FoxM1 is an important regulator of cyst growth in ADPKD. FoxM1 is upregulated in cyst-lining epithelial cells in Pkd1 mutant mouse kidneys and human ADPKD kidneys. FoxM1 promotes cystic renal epithelial cell proliferation by increasing the expression of Akt and Stat3 and the activation of ERK and Rb. FoxM1 also regulates cystic renal epithelial cell apoptosis through NF-κB signaling pathways. In addition, FoxM1 regulates the recruitment and retention of macrophages in Pkd1 mutant mouse kidneys, a process that is associated with FoxM1-mediated upregulation of monocyte chemotactic protein 1. Targeting FoxM1 with its specific inhibitor, FDI-6, delays cyst growth in rapidly progressing and slowly progressing Pkd1 mutant mouse kidneys. This study suggests that FoxM1 is a central and upstream regulator of ADPKD pathogenesis and provides a rationale for targeting FoxM1 as a therapeutic strategy for ADPKD treatment.
Numerical methods and hypoexponential approximations for gamma distributed delay differential equations
Authors: Cassidy Tyler , Gillich Peter , Humphries Antony R , van Dorp Christiaan H
Published: November 2022

Gamma distributed delay differential equations (DDEs) arise naturally in many modelling applications. However, appropriate numerical methods for generic gamma distributed DDEs have not previously been implemented. Modellers have therefore resorted to approximating the gamma distribution with an Erlang distribution and using the linear chain technique to derive an equivalent system of ordinary differential equations (ODEs). In this work, we address the lack of appropriate numerical tools for gamma distributed DDEs in two ways. First, we develop a functional continuous Runge–Kutta (FCRK) method to numerically integrate the gamma distributed DDE without resorting to Erlang approximation. We prove the fourth-order convergence of the FCRK method and perform numerical tests to demonstrate the accuracy of the new numerical method. Nevertheless, FCRK methods for infinite delay DDEs are not widely available in existing scientific software packages. As an alternative approach to solving gamma distributed DDEs, we also derive a hypoexponential approximation of the gamma distributed DDE. This hypoexponential approach is a more accurate approximation of the true gamma distributed DDE than the common Erlang approximation but, like the Erlang approximation, can be formulated as a system of ODEs and solved numerically using standard ODE software. Using our FCRK method to provide reference solutions, we show that the common Erlang approximation may produce solutions that are qualitatively different from the underlying gamma distributed DDE. However, the proposed hypoexponential approximations do not have this limitation. Finally, we apply our hypoexponential approximations to perform statistical inference on synthetic epidemiological data to illustrate the utility of the hypoexponential approximation.
Matroid Stratifications of Hypergraph Varieties, Their Realization Spaces, and Discrete Conditional Independence Models
Authors: Clarke Oliver , Grace Kevin , Mohammadi Fatemeh , Motwani Harshit J
Published: November 2022

We study varieties associated to hypergraphs from the point of view of projective geometry and matroid theory. We describe their decompositions into matroid varieties, which may be reducible and can have arbitrary singularities by the Mnëv–Sturmfels universality theorem. We focus on various families of hypergraph varieties for which we explicitly compute an irredundant irreducible decomposition. Our main findings in this direction are three-fold: (1) we describe minimal matroids of such hypergraphs; (2) we prove that the varieties of these matroids are irreducible and their union is the hypergraph variety; and (3) we show that every such matroid is realizable over real numbers. As corollaries, we give conceptual decompositions of various, previously studied, varieties associated with graphs, hypergraphs, and adjacent minors of generic matrices. In particular, our decomposition strategy gives immediate matroid interpretations of the irreducible components of multiple families of varieties associated to conditional independence models in statistical theory and unravels their symmetric structures which hugely simplifies the computations.
Time Zero Regularity of Ricci Flow
Authors: Lee Man-Chun , Topping Peter M
Published: November 2022

We consider the problem of when a smooth Ricci flow, for positive time, that attains smooth initial data in a weak sense must be smooth down to the initial time. We obtain curvature estimates for an example where this fails that was given in [26]. We prove a positive result in the case that the flow satisfies a lower ${ {\textrm {K}_{\textrm {IC}_1}}}$ curvature bound, equivalent to a lower Ricci bound in three dimensions. As an application, we prove that Gromov–Hausdorff limits of WPIC1 manifolds are WPIC1.
Manufacture, development, and application of sensor-enabled geosynthetics: state-of-the-art review
Authors: Wang Yilin , Cui Xinzhuang , Liu Kaiwen , Jiang Peng
Published: November 2022

The long-term in situ monitoring of transportation infrastructure is a key necessity for intelligent traffic management, which requires the monitoring methods to have good performances on the distributed measurements, durability, robustness, and convenience. To offer an alternative for intelligent monitoring of transportation infrastructures, this paper introduces the development and application of an innovative material named sensor-enabled geosynthetics (SEG) derived from the tensoresistivity of conductive polymers. Unlike other monitoring media, the unique feature of the SEG is its two-fold function: in situ reinforcement and monitoring. The manufacturing process of SEG is introduced and the basic properties of SEG are investigated by laboratory tests. The corresponding constitutive models are established and employed in the theoretical analysis of SEG interacting with soil. Based on the experimental and theoretical approaches, a positioning, precursor identification and early warning method for the internal failure of subgrade is proposed and incorporated into the safety monitoring and early warning system for geotechnical engineering involving SEG. According to the application cases of SEG and the system in highway engineering, SEG is proved to perform excellently in terms of the durability, distributed measurements, wide measuring range, and negligible installation effect. Thus, it is considered as an innovative and reliable alternative for long-term in situ monitoring of transportation infrastructures particularly in subgrade engineering.
The Genre View of Public Lands: The Case of National Monuments
Authors: Tenen Levi
Published: November 2022

In this article, I begin developing what I call the genre view of public lands. It holds that public land designations fall into different genres of land management. I focus on one designation in particular—US national monuments created under the Antiquities Act—to develop the view and illustrate its significance. I characterize the national monument genre in terms of two norms stated in the Act and show how they shape public space in distinctive ways. I then illustrate how the genre view opens avenues for evaluating land designations. By way of example, I evaluate national monuments according to aesthetic considerations. I argue that the genre is, perhaps surprisingly, aesthetically vexed and that there is an aesthetic reason for presidents to depart from the original intent and meaning of the Act. This also lends support for some of the most controversial national monuments. Drawing from case law, I then show how aesthetic evaluations may hold legal weight. Such considerations can also influence decisions about whether to protect an area as a monument. In these ways, the genre view offers a framework for philosophers, and particularly aestheticians, to contribute to environmental law and policy.
A preliminary study on the potential of FT-IR spectroscopy and chemometrics for tracing the geographical origin of Moroccan virgin olive oils
Authors: Laouni Amine , El Orche Aimen , Elhamdaoui Omar , Karrouchi Khalid , El Karbane Miloud , Bouatia Mustapha
Published: November 2022

Objective

This study aims on the one hand to study the physicochemical data of olive oils collected from six regions of Morocco during two consecutive years 2020 and 2021.

Methods

Fourier transform infrared spectroscopy (FTIR) was used in this study as an emerging analytical technique to express a unique "fingerprint". A preliminary processing of the ATR-FTIR spectral data was performed by preprocessing algorithm in order to reduce the noise, the effect of signal variation and minimize the effects of light scattering to extract the maximum analytical information from the spectra. A multivariate statistical procedure based on principal component analysis (PCA) coupled with linear discriminant analysis (LDA) as well as partial least squares discriminant analysis (PLS-DA) were developed to provide a powerful classification approach.

Results

Based on principal component analysis (PCA), six clusters were identified. The application of PCA-LDA and PLS-DA procedures demonstrate a powerful capacity in predicting the geographic origin of olive oils, this capacity is showed by the high value of CCR varying between 84.09% and 100%.

Conclusion

The suggested procedure has given reliable results for the classification of olive oils according to their geographical origin, with advantages such as being fast, inexpensive and not requiring any prior separation process.

Highlight

The performance of this approach is significantly faster and possesses a higher degree of selectivity and sensitivity. The Implementation of this technique for routine analysis of olive oil would save significant time, resources and solvents.
Tailoring Two Chemometric Models for Determination of Three Neuromuscular Combined Medications and Application to Spiked Human Plasma
Authors: Abdelhamid Nessreen S , Farid Nehal F , Anwar Basma H , Magdy Maimana A
Published: November 2022

Background

Prednisolone, 6-mercaptopurine, and pyridostigmine bromide are co-administered together to treat a neuromuscular autoimmune disease called myasthenia gravis. Prednisolone and 6-mercaptopurine are immunosuppressant drugs. 6-Mercaptopurine is the active form of the pro-drug azathioprine. Pyridostigmine bromide is a cholinesterase enzyme inhibitor. Curently, green characteristics are taken into account by analysts when they develop new methods.

Objective

The spectra of the three compounds and plasma are highly overlapped, so this study aims to remove this overlap and determine the three components quantitatively in raw powders and spiked human plasma using green methods.

Methods

Two multivariate updated chemometric models called principle component analysis and partial least-squares were developed. Three greenness assessment tools: the eco-scale, the analytical greenness metric approach, and the green analytical method index, were used to evaluate the greenness behavior of the generated models.

Results

The two models were verified in accordance with Food and Drug Administration requirements, and the results were within acceptable limits. In addition they are relatively green in accordance with the abovementioned greenness evaluation tools.

Conclusion

The developed models succeeded in determining the proposed drugs in their tertiary combinations and spiked human plasma with satisfactory precision, accuracy, and good greenness behavior.

Highlights

Two ecologically evaluated, multivariate spectrophotometric methods were developed for the determination of pyridostigmine bromide, 6-mercaptopurine, and prednisolone in spiked human plasma.
Minimal Rickettsial Infection Rates and Distribution of Ticks in Uganda: An Assessment of the Seasonal Effects and Relevance to Tick-Borne Disease Risk in East Africa
Authors: Corrigan James , Marion Brianna , English James , Eneku Wilfred , Weng Ju Lin , Rugg Molly , Dotrang Thoai , Dunford James , Byaruhanga Anatol M , Byarugaba Denis K , Ramalho-Ortigao Marcelo , Wanja Elizabeth W
Published: November 2022

Tick-borne diseases (TBDs) pose a significant risk to humans and represent one of the major factors influencing readiness within the United States’ military worldwide. Additionally, ticks and TBDs constitute major animal health problems leading to economic losses at multiple levels affecting low- and middle-income countries the hardest. Tick control is frequently hampered by issues ranging from acaricide resistance to lack of data on tick distribution and infection rates. We conducted a cross-sectional study to assess tick species distribution, host use, and rickettsial pathogen infection rate of ticks in different areas of the Uganda Cattle Corridor. We identified 4,425 hard ticks (Ixodida: Ixodidae) comprised of seven species by morphological characters with 3,315 ticks collected from four locations during the dry season and 1,110 ticks from one location during the wet season. Rickettsial pathogen prevalence was assessed in ticks collected from two districts to determine the minimum infection rate compared across seasons, village location, and tick species. We found statistically significant differences in the abundance and distribution of tick species among districts in the dry season, host animal species, and the proportion of rickettsial positive pools between villages. Seasonality, village location, and tick species do not affect the minimum infection rate of rickettsial pathogens of ticks in Uganda, but village location affects the proportion of positive tick pools. These results indicate geographical and seasonal differences among pathogen-harboring ticks contributing to our understanding of the current distribution of ticks and TBDs in Uganda.
Complexity function and complexity of validity of modal and superintuitionistic propositional logics
Authors: Rybakov Mikhail , Shkatov Dmitry
Published: November 2022

We consider the relationship between the algorithmic properties of the validity problem for a modal or superintuitionistic propositional logic and the size of the smallest Kripke countermodels for non-theorems of the logic. We establish the existence, for every degree of unsolvability, of a propositional logic whose validity problem belongs to the degree and whose every non-theorem is refuted on a Kripke frame that validates the logic and has the size linear in the length of the non-theorem. Such logics are obtained among the normal extensions of the propositional modal logics $\textbf {KTB}$, $\textbf {GL}$ and $\textbf {Grz}$ as well as in the lattice of superintuitionistic propositional logics. This shows that the computational complexity of a modal or superintuitionistic propositional logic is, in general, not related to the size of the countermodels for its non-theorems.
Theory of Planned Behavior and Active Duty Air Force Members’ Mental Health Help-Seeking
Authors: Engelhardt Ethan C , Bicknell Graeme , Oliver Mark , Flaherty Chris , Line Katelynn , King Erika
Published: November 2022

Introduction

Although military members often encounter significant atypical stressors while serving, many service members are still reluctant to seek mental health (MH) treatment. Help-seeking behavior for MH needs is a rising concern for active duty Air Force personnel. Conditions such as post-traumatic stress disorder, depression, anxiety, and substance abuse are just a few issues that military members deal with, but things like stigma, attitudes toward MH, and behavioral control might keep these individuals from seeking services. This study utilizes the theory of planned behavior (TPB) to identify better and understand barriers to the help-seeking behavior of active duty Air Force members.

Materials and Methods

The 2017 Air Force Community Feedback Tool was used for this study. This confidential survey was completed by a large sample of the military population (N = 10,705). The survey was used to examine relationships between the TPB-related variables and respondents with mood problems identifying a need for professional counseling, seeking MH services, and reporting that the services met their needs. Multiple linear and binary logistic regression models were utilized to analyze findings from this sample.

Results

This study highlights how attitudes, subjective norms, and perceived behavioral control impact help-seeking behavior for these individuals. Findings include the MH providers’ good reputations, wait times for services, ease of access to care, and negative experiences with supervisor permission, all of which showed a statistically significant impact on help-seeking behavior. Dependent variables included “I need professional counseling,” “I contacted a MH care provider in the past year to try to meet this need,” and “How much the MH care provider helped you meet your needs.” Each of these variables had statistically significant relationships with the connecting variables of the TPB.

Conclusions

Findings from this study reveal how attitudes, subjective norms, and perceived behavioral control play an essential role in an active duty Air Force member’s decision to seek help for MH concerns. This study suggests that active duty military members are less concerned about the belief that seeking MH care could harm their reputations and more aware of the potential negative reputations of MH clinics. Finally, actionable steps are outlined to better support help-seeking behavior, which might be recommended to better train and encourage military leaders to address the MH needs of themselves and the members of their units.
Immunoglobulin somatic hypermutation in a defined biochemical system recapitulates affinity maturation and permits antibody optimization
Authors: Jeong Soo Lim , Zhang Hongyu , Yamaki Shanni , Yang Chenyu , McKemy David D , Lieber Michael R , Pham Phuong , Goodman Myron F
Published: November 2022

We describe a purified biochemical system to produce monoclonal antibodies (Abs) in vitro using activation-induced deoxycytidine deaminase (AID) and DNA polymerase η (Polη) to diversify immunoglobulin variable gene (IgV) libraries within a phage display format. AID and Polη function during B-cell affinity maturation by catalyzing somatic hypermutation (SHM) of immunoglobulin variable genes (IgV) to generate high-affinity Abs. The IgV mutational motif specificities observed in vivo are conserved in vitro. IgV mutations occurred in antibody complementary determining regions (CDRs) and less frequently in framework (FW) regions. A unique feature of our system is the use of AID and Polη to perform repetitive affinity maturation on libraries reconstructed from a preceding selection step. We have obtained scFv Abs against human glucagon-like peptide-1 receptor (GLP-1R), a target in the treatment of type 2 diabetes, and VHH nanobodies targeting Fatty Acid Amide Hydrolase (FAAH), involved in chronic pain, and artemin, a neurotropic factor that regulates cold pain. A round of in vitro affinity maturation typically resulted in a 2- to 4-fold enhancement in Ab-Ag binding, demonstrating the utility of the system. We tested one of the affinity matured nanobodies and found that it reduced injury-induced cold pain in a mouse model.
UBE2T promotes breast cancer tumor growth by suppressing DNA replication stress
Authors: Dutta Roshan , Guruvaiah Praveen , Reddi Kiran Kumar , Bugide Suresh , Reddy Bandi Dhana Sekhar , Edwards Yvonne J K , Singh Kamaljeet , Gupta Romi
Published: November 2022

Breast cancer is a leading cause of cancer-related deaths among women, and current therapies benefit only a subset of these patients. Here, we show that ubiquitin-conjugating enzyme E2T (UBE2T) is overexpressed in patient-derived breast cancer samples, and UBE2T overexpression predicts poor prognosis. We demonstrate that the transcription factor AP-2 alpha (TFAP2A) is necessary for the overexpression of UBE2T in breast cancer cells, and UBE2T inhibition suppresses breast cancer tumor growth in cell culture and in mice. RNA sequencing analysis identified interferon alpha–inducible protein 6 (IFI6) as a key downstream mediator of UBE2T function in breast cancer cells. Consistently, UBE2T inhibition downregulated IFI6 expression, promoting DNA replication stress, cell cycle arrest, and apoptosis and suppressing breast cancer cell growth. Breast cancer cells with IFI6 inhibition displayed similar phenotypes as those with UBE2T inhibition, and ectopic IFI6 expression in UBE2T-knockdown breast cancer cells prevented DNA replication stress and apoptosis and partly restored breast cancer cell growth. Furthermore, UBE2T inhibition enhanced the growth-suppressive effects of DNA replication stress inducers. Taken together, our study identifies UBE2T as a facilitator of breast cancer tumor growth and provide a rationale for targeting UBE2T for breast cancer therapies.
Laser hyperthermia: Past, present, and future
Authors: Schupper Alexander J , Chanenchuk Tori , Racanelli Anna , Price Gabrielle , Hadjipanayis Constantinos G
Published: November 2022

Magnetic resonance imaging-guided laser interstitial thermal therapy (LITT) is an ablative procedure using heat from a laser to provide cytoreduction in tissue. It is a minimally invasive procedure that has been used in intracranial pathologies such as high-grade gliomas, metastatic lesions, epilepsy, and other lesions. While LITT may offer a more acceptable complication profile compared to open surgery, the role of laser therapy for intracranial lesions in current treatment paradigms continues to evolve. This review will focus on the background and application of LITT, the current evidence for its use, and future directions for the technology.
Risk Factors for Severe Coronavirus Disease 2019 Among Human Immunodeficiency Virus-Infected and -Uninfected Individuals in South Africa, April 2020–March 2022: Data From Sentinel Surveillance
Authors: Walaza Sibongile , Tempia Stefano , von Gottberg Anne , Wolter Nicole , Bhiman Jinal N , Buys Amelia , Amoako Daniel , Moosa Fahima , du Plessis Mignon , Moyes Jocelyn , McMorrow Meredith L , Dawood Halima , Variava Ebrahim , Reubenson Gary , Nel Jeremy , Zar Heather J , Makhasi Mvuyo , Meiring Susan , Quan Vanessa , Cohen Cheryl
Published: November 2022

Background

Data on risk factors for coronavirus disease 2019 (COVID-19)-associated hospitalization and mortality in high human immunodeficiency virus (HIV) prevalence settings are limited.

Methods

Using existing syndromic surveillance programs for influenza-like-illness and severe respiratory illness at sentinel sites in South Africa, we identified factors associated with COVID-19 hospitalization and mortality.

Results

From April 2020 through March 2022, severe acute respiratory syndrome coronavirus 2 was detected in 24.0% (660 of 2746) of outpatient and 32.5% (2282 of 7025) of inpatient cases. Factors associated with COVID-19-associated hospitalization included the following: older age (25–44 [adjusted odds ratio {aOR}= 1.8, 95% confidence interval (CI) = 1.1–2.9], 45–64 [aOR = 6.8, 95% CI = 4.2–11.0] and ≥65 years [aOR = 26.6, 95% CI = 14.4–49.1] vs 15–24 years); black race (aOR, 3.3; 95% CI, 2.2–5.0); obesity (aOR, 2.3; 95% CI, 1.4–3.9); asthma (aOR, 3.5; 95% CI, 1.4–8.9); diabetes mellitus (aOR, 5.3; 95% CI, 3.1–9.3); HIV with CD4 ≥200/mm3 (aOR, 1.5; 95% CI, 1.1–2.2) and CD4 <200/mm3 (aOR, 10.5; 95% CI, 5.1–21.6) or tuberculosis (aOR, 12.8; 95% CI, 2.8–58.5). Infection with Beta (aOR, 0.5; 95% CI, .3–.7) vs Delta variant and being fully vaccinated (aOR, 0.1; 95% CI, .1–.3) were less associated with COVID-19 hospitalization. In-hospital mortality was increased in older age (45–64 years [aOR, 2.2; 95% CI, 1.6–3.2] and ≥65 years [aOR, 4.0; 95% CI, 2.8–5.8] vs 25–44 years) and male sex (aOR, 1.3; 95% CI, 1.0–1.6) and was lower in Omicron-infected (aOR, 0.3; 95% CI, .2–.6) vs Delta-infected individuals.

Conclusions

Active syndromic surveillance encompassing clinical, laboratory, and genomic data identified setting-specific risk factors associated with COVID-19 severity that will inform prioritization of COVID-19 vaccine distribution. Elderly people with tuberculosis or people with HIV, especially severely immunosuppressed, should be prioritized for vaccination.
Health and Digital Technology Partnerships
Authors: Specker Sullivan Laura
Published: November 2022

Abstract: Digital technology companies are seeking out partnerships with medical institutions at an astounding rate. Those involved tout these partnerships as empowering consumers, driving innovation, and increasing efficiency. At the same time, ethical red flags have gone up over potential violations of patient privacy and unsanctioned use of data for non-medical purposes. While contract transparency is a core ethical concern when personal health data is involved, a broader question is whether these contracts are different in kind than more established healthcare partnerships. Big data partnerships are relatively unique; these companies neither specialize in the healthcare industry nor provide healthcare institutions with an identifiable medical product. The ethical dimensions of these partnerships extend to broader questions about the appropriate role of digital technology corporations in an arena that, at least in theory, is oriented toward the physical, mental, and social well-being of everyone within our society.
The pattern of cortical thickness underlying disruptive behaviors in Alzheimer's disease
Authors: Xiong Raymond M , Xie Teng , Zhang Haifeng , Li Tao , Gong Gaolang , Yu Xin , He Yong
Published: November 2022

Background

Disruptive behaviors, including agitation, disinhibition, irritability, and aberrant motor behaviors, are commonly observed in patients with Alzheimer's disease (AD). However, the neuroanatomical basis of these disruptive behaviors is not fully understood.

Objective

To confirm the differences in cortical thickness and surface area between AD patients and healthy controls and to further investigate the features of cortical thickness and surface area associated with disruptive behaviors in patients with AD.

Methods

One hundred seventy-four participants (125 AD patients and 49 healthy controls) were recruited from memory clinics at the Peking University Institute of Sixth Hospital. Disruptive behaviors, including agitation/aggression, disinhibition, irritability/lability, and aberrant motor activity subdomain scores, were evaluated using the Neuropsychiatry Inventory. Both whole-brain vertex-based and region-of-interest-based cortical thickness and surface area analyses were automatically conducted with the CIVET pipeline based on structural magnetic resonance images. Both group-based statistical comparisons and brain-behavior association analyses were performed using general linear models, with age, sex, and education level as covariables.

Results

Compared with healthy controls, the AD patients exhibited widespread reduced cortical thickness, with the most significant thinning located in the medial and lateral temporal and parietal cortex, and smaller surface areas in the left fusiform and left inferior temporal gyrus. High total scores of disruptive behaviors were significantly associated with cortical thinning in several regions that are involved in sensorimotor processing, language, and expression functions. The total score of disruptive behaviors did not show significant associations with surface areas.

Conclusion

We highlight that disruptive behaviors in patients with AD are selectively associated with cortical thickness abnormalities in sensory, motor, and language regions, which provides insights into neuroanatomical substrates underlying disruptive behaviors. These findings could lead to sensory, motor, and communication interventions for alleviating disruptive behaviors in patients with AD.
Credit Environment and Small Business Dynamics: Evidence from Establishment-Level Data
Authors: Lin Chen , Tai Mingzhu , Xie Wensi
Published: November 2022

We evaluate how a positive, technology-driven shock to bank liquidity affects small business dynamics across different size distributions. We first show that banks receiving positive liquidity shocks increase lending to relatively larger SMEs, not to the smallest firms. This finding is consistent with the view that a positive liquidity shock enhances bank charter values, thereby reducing risk-taking incentives. Moreover, such disproportionate credit allocation leads to a crowding-out effect on micro firms. When larger SMEs grow faster and exit less because of better access to credit, their expansion stifles the development of micro firms, whose access to credit remains unchanged. (JEL G21, J21, L22)
Escaping Air Pollution: Immigrants, Students, and Spillover Effects on Property Prices Abroad
Authors: Chang Yuk Ying , Dasgupta Sudipto
Published: November 2022

We construct a time series of news coverage about air pollution in China for the period 1977–2019. Our measure of abnormal news coverage (ANC) of China’s air pollution is uncorrelated with growth in economic activity or cyclical components of such activity, but strongly correlated with weather-related and atmospheric conditions known to cause air pollution. ANC is associated with more capital flight from China. Focusing on the USA as a destination country, we find that ANC is associated with more Chinese citizens emigrating to US regions with stronger ethnic links to China, and more international students enrolling in US institutions with stronger Chinese student links. US regions with stronger ethnic or educational ties to China experience higher property price growth when ANC is higher. Our study suggests that perception of local environmental risk can have major consequences for the cross-border reallocation of capital and labor.
ANALYSES OF SOME CALL FACTORS AFFECTING SAR LEVELS OF GSM MOBILE PHONES USED IN GHANA
Authors: Osei S , Amoako J K , Sam F , Onyekwere P , Kudozia R Y
Published: November 2022

In response to mounting radiofrequency health concerns, this study was constituted to provide critical scientific data and assess any potential exposure from global system for mobile communication mobile phones. Specific absorption rate (SAR) from phones approved by the regulator and untested/unapproved phones were measured with a ComoSAR system. The maximum 10 g SAR (0.51 W/kg) and 1 g SAR (0.99 W/kg) measured were 25 and 62% of the International Commission on Non-Ionizing Radiation Protection and Federal Communication Commission limits, respectively. The approved phone produced statistically significant higher SAR values relative to the untested phone. SAR values of the right ear were relatively higher. All maximum SAR values were recorded on the right ear. The regulatory approval status of the phone, phone’s orientation to the head, operating frequency channel and in which ear (right or left) the phone is used influenced the SAR measured. The SAR values of the approved phone compared favourably with similar studies while the unapproved phone does not.